Hampered by a right calf issue since early last month, Hynes is the only player on either Origin side who has not been named in the extended squad for their side's game this weekend - other than players whose teams have the bye.
The Sharks will instead start Braydon Trindall and Daniel Atkinson in the halves for Saturday night's clash at Suncorp Stadium and spare Hynes from playing on the trip to Brisbane.
Hynes' club and state teammate Cam McInnes has been named to back up from his Origin debut, pushing Jack Williams to the bench.
It comes after Hynes entered camp for Wednesday's series opener under an injury cloud, but managed to allay concerns as to his fitness and firm for a second Blues cap.
Nicho Hynes will miss Cronulla's next game against the Broncos. (Dave Hunt/AAP PHOTOS)
The Broncos' Kotoni Staggs returns from a rib injury to line up in the centres for the game.
After a quad strain cruelly denied him his Origin debut, Dylan Edwards has been named in the reserves for Penrith so could make a late charge into the 17 for Sunday's clash against Manly.
Edwards remains in the NSW camp and is yet to return to the Panthers since suffering his injury on Saturday so will be assessed ahead of the game.
Penrith have named Moses Leota despite the triple premiership-winning prop leaving last week's loss to St George Illawarra with a hamstring concern.
The Sea Eagles have kept recent debutant Lehi Hopoate at fullback, meaning Tolu Koula will play in the centres on his return from a shoulder injury.
Elsewhere, South Sydney will play Cody Walker and Jack Wighton together in the halves for the first time after the former recovered from the minor calf issue that scuppered his NSW chances.
Cody Walker is glad to be back after missing Souths' round-12 win over Parramatta. (Dean Lewins/AAP PHOTOS)
Walker returns for the Rabbitohs' clash with a Gold Coast side that has crafty fullback Jayden Campbell back from a knee injury and veteran Kieran Foran on deck after his hamstring issue.
Warriors prop Addin Fonua-Blake returns to face North Queensland on Saturday night after the club stood him down in round 12 for a dressing room walkout the weekend prior.
The star prop headlines a long list of ins for the Kiwi side, who also welcome back captain Tohu Harris (wrist) Wayde Egan (head knock), Charnze Nicoll-Klokstad (illness), Rocco Berry (hand) and Kurt Capewell (calf).
Halfback Shaun Johnson is still at least another week off returning from his pectoral injury, though.
Parramatta rookie Blaize Talagi comes into the Eels' backline to face Canterbury after the club confirmed Bailey Simonsson would miss the remainder of the season with an anterior cruciate ligament injury.
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