Nadal dragged the hostility off the court with him when he proceeded to take a shot at Kyrgios in his post-match media conference.
He said Kyrgios "lacked respect" after the pair clashed over a time wasting accusation.
Kyrgios eventually claimed an unforgettable 3-6 7-6 (7-2) 7-6 (8-6) win after a rollercoaster three hours.
It was everything that makes Kyrgios one of the best shows in tennis.
Nadal even served for the match in the tiebreak while leading 6-5. The World No. 2 inexplicably double faulted to give Kyrgios a 7-6 lead. Kyrgios then served it out in unbelievable scenes.
Kyrgios was booed by fans throughout the match and he was more than a little animated after saving three-match points and serving out the match.
He fell to the floor after a Nadal groundstroke sailed long on match point and he then charged to the net while pumping his arms towards the crowd.
The crowd continued to boo the Aussie, even as he and Nadal shook hands at the net.
The pair only shared a brief, token exchange at the net which appeared more than a little frosty after such a fierce contest.
Nadal was still angry about the contest in his post match press conference, declaring Kyrgios "lacks respect" for his opponents and the crowd.
"He's a player who has enormous talent, could be winning grand slams or fighting for the No. 1 ranking," Nadal said in Spanish.
"He lacks respect for the crowd, his opponent and towards himself."
He went on to say: "I don't think he's a bad guy, but he lacks a little respect for the public and the rival".
Nadal appeared to be offended in the tense third set tiebreak when Kyrgios complained to the chair umpire about Nadal taking too long in between points when Kyrgios was serving.
At 6-4 in the breaker, ahead of Nadal's second match point, the Spaniard stuck his racquet into the air to inform Kyrgios he wasn't ready to play the next point.
Kyrgios was not happy that he couldn't play with his natural serve rythm and appeared to tell the umpire that it was his right while serving to decide how long the break should be in between points.
It was just one of many moments where the pro-Nadal crowd jeered Kyrgios.
The Canberra product even gave it back to them after Nadal had left the court, sticking his hand up to his ear as sections of the crowd booed, further antagonising them.
Kyrgios responded to Nadal's criticism by saying he would not be giving the advice any consideration.
"He doesn't know the journey I've been through," Kyrgios said.
"He doesn't know anything about me. So, I'm not going to listen at all. That's the way I play.
"The way he plays is very slow in between points. The rule in the book says he has to pay to the speed of the server, but Rafa has his speed every time, so I'm not going to comment on him.
"He's got his own game. I've got my game. We played well. That's the sport. People are different so I'm not going to take that into consideration at all."
Kyrgios said he still considers Nadal one of the best players of all time.
"I've had a tough year so far. I started with some injuries," he said.
"I love playing Rafa, he's an unbelievable champion. Anyway I just love going out there and playing in big matches. I feel really good. To be able to trust my body to get wins like this is pretty important.
"It was one of the best atmosphere's I've ever played in. The majority of the crowd were going for Rafa. He's going to get that wherever he goes. He's an unbelievable player. One of the greatest of all time. So just to be able to be a part of that atmosphere… it was a match that I'll never, ever forget."
Nadal's scathing response has cast a shadow over Kyrgios' epic fightback.
The win gives Kyrgios a perfect 5-0 record against Nadal in tiebreaks and sets up another salivating clash between him and Stan Wawrinka in the quarter-finals.
It was arguably Kyrgios' best win in two years.
He joins fellow Australians Alex de Minaur and John Millman in the quarter-finals.
Criticised for a perceived lack of effort in some matches this year, Kyrgios stayed focused after giving up the opening set.
He saved nine break points throughout the match including coming back from 0-40 positions in the final two sets.
Nadal, who wasn't broken in the match, looked set to triumph when up 6-3 in the deciding tiebreaker.
But Kyrgios saved three match points, including one with a lunging volley that hit the net cord and just landed in.
Kyrgios' impressive fightback stunned the tennis world.
He suffered a crazy brain snap in the third set when he attempted to underarm serve while Nadal was still standing miles behind the baseline — anticipating another booming Kyrgios first serve.
As only Kyrgios can do, the Aussie went on to win that service game, despite his underarm serve, and went on to force the match in the a third set tiebreak as the match ticked over the three hour mark.
It was a match of epic proportions where the crowd went from Heckling Kyrgios early, to chanting his name and then booing him again as he roared back into the contest.
Kyrgios earlier was heard complaining to the chair umpire throughout the first set that he was not feeling well.
After dropping the opening set 6-3, Kyrgios called for a trainer and took a medical timeout, complaining of back pain.
Courtside microphones pick up an exchange between Kyrgios and the trainer where the former Aussie No. 1 was heard telling the physiotherapist that retiring was not an option for him because of the backlash it would create.
"If I forfeit, the media will blow it up…. I'll be booed off the court," he said.
He was also heard getting up to his old tricks, screaming at fans in the Acupulco crowd with several Tennis commentators on Twitter claiming Kyrgios swore at one group of fans.
Meanwhile, Millman moved through to he last eight withan emphatic straight-sets victory over German Peter Gojowczyk.
Millman blitzed the world No.87, 6-0 6-2, at one stage winning eight games in succession.
The world No. 44 converted six break points and delivered the contest's only two aces to set up a quarter-final clash with third-seed John Isner.
Big-serving American Isner eliminated compatriot Sam Querrey 6-4 6-4. Millman's win was his second comfortable triumph — the eighth seed beat Spaniard Marcel Granollers 6-3 6-4 in the opening round.
Fifth seed Alex de Minaur boosted Australia's presence in the quarter-finals when Feliciano Lopez (Spain) withdrew before their second round match. Wawrinka also beat seventh-seeded American Steve Johnson 7-6 (7-5) 6-4 to progress to the last eight.
