Stosur's half of the draw looks better by the day with her nemesis Maria Sharapova, who enjoys a 9-0 record against her, joining eighth seed Marion Bartoli and Venus Williams on the departure list. However, Stosur was hardly going to be looking too far ahead following her close shave and her early exits at the French Open and Wimbledon this year.
"I think even though some of the big names are out, someone beat those big names too," she said. "Flavia Pennetta [who defeated Sharapova] is a great player and she is always tough to beat. Even though Maria has gone, it does not mean that it is a walk in the park."
Stosur enjoys a 3-2 edge over Kirilenko and won their most recent meeting in 2009, 6-2 6-4 on hardcourt in Los Angeles. The winner of that round of 16 encounter will take on the winner of Sabine Lisicki and world No 2 Vera Zvonareva, two players Stosur has a brilliant record against.
Meanwhile, Sharapova's undefeated record in three-set matches ended yesterday and so did her stay at the US Open.
No 26 seed Pennetta of Italy knocked out the 2006 champion 6-3 3-6 6-4 in the third round to hand Sharapova her first loss in 13 three-set matches this year.
"She's a good fighter," said Pennetta, who conceded she didn't know about Sharapova's record in three-setters.
"You can never give up with her. You have to be focused until the last game, until the last point, actually."
Sharapova made 12 double-faults, including two in the last game. She did not look sharp over a two-hour, 29-minute match that featured plenty of nervous tennis. Sharapova made 60 unforced errors, and lost four break points while trailing 2-0 in the third set.
"I didn't feel comfortable with most of my game today," Sharapova said.
Pennetta, who also had a big win in Arthur Ashe Stadium two years ago in the round of 16 against Vera Zvonareva, called this one of the biggest victories of her career.
"But it's just a match," she said. "It's over and I have to be focused on the next one."
Pennetta's round of 16 match is against No 13 Peng Shuai of China, who defeated No 19 Julia Goerges of Germany 6-4 7-6 (1).
The loss by third-seeded Sharapova, the runner-up at Wimbledon this year, kicked yet another top player out of a wide-open draw. Already, the defending Wimbledon and French Open champions have been dispatched and two-time defending US Open champion Kim Clijsters didn't enter because of injury.
Earlier, No 2 Vera Zvonareva defeated No 30 Anabel Medina Garrigues and No 1 Caroline Wozniacki is still in the draw, but neither has won a Grand Slam title.