Cook apart, second rower Leivaha Pulu and centre Anthony Gelling are included on the extended eight-man bench along with front rower Agnatius Paasi, who played one NRL game for the Warriors in 2014 before making 54 appearances for the Titans from 2015-2017.
Ligi Sao comes in to replace veteran back rower Simon Mannering, who could be out for a few weeks with a shoulder injury.
James Gavet partners veteran acquisition Blair in the front row.
Halves Shaun Johnson and Green will have their first NRL start together, as will Hiku and Mate Ma's wing David Fusitu'a on the right flank.
The Warriors will be looking to end a miserable Perth hoodoo on Saturday.
They have yet to win in Western Australia in nine previous attempts, and the city has been the scene of some of the club's most dispiriting losses, including the 2012 reversal against Manly, when the Warriors gave up an 18-0 lead.
The Auckland club will also need to end a poor record against the Rabbitohs, who they haven't beaten in their last six encounters.
Warriors head coach Stephen Kearney was especially pleased for Cook, who has come through the club's youth system
"It's really special being able to name Sam," said Kearney
"He's had a wonderful pre season and he has worked really hard for the last 15 or so weeks. He had some nice touches in the trials and gets his opportunity to make his debut.
"Our new players have fitted in wonderfully well, too, and I'm really excited about seeing them play on Saturday. Simon picked up a shoulder injury in our last trial which could keep him out for a few weeks but young Isaiah Papali'i has had a great pre season and he'll do a good job."
The Warriors' match is the first leg of the Perth NRL double header which is rounded out by the 2017 premiers Melbourne Storm facing Canterbury-Bankstown (11.05pm NZT).
Warriors v South Sydney Rabbitohs
Perth Stadium, Perth
9.00pm, Saturday, March 10, 2018
Warriors
1Roger Tuivasa-Sheck (c)
2David Fusitu'a
3Peta Hiku
4Solomone Kata
5Ken Maumalo
6Blake Green
7Shaun Johnson
8James Gavet
9Issac Luke
10Adam Blair
11Isaiah Papali'i
12Tohu Harris
13Ligi Sao
Interchange
14Sam Cook
15Leivaha Pulu
16Sam Lisone
17Bunty Afoa
18Jazz Tevaga
20Mason Lino
21Agnatius Paasi
22Anthony Gelling
Head Coach | Stephen Kearney
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