Latrell Mitchell will play five-eighth and Blaize Talagi will finally have a chance to start at Penrith as the NRL undergoes a halves shake-up in round six.

Hamstring injuries to Cody Walker and Jamie Humphreys have left Mitchell to partner Jayden Sullivan in South Sydney's halves to face North Queensland in Perth on Saturday.

It means Mitchell will go a second-straight week out of his preferred fullback spot, having returned from injury to start in the centres last week.

But coach Wayne Bennett had few options for this week's game, given a NSW Cup suspension has denied big-money recruit Lewis Dodd the chance for a debut, and Josh Schuster is still working back to fitness.

Bennett has received a boost in his outside backs, though, as Alex Johnston and Euan Aitken return from injury, with the former resuming his pursuit of the NRL's all-time try-scoring record.

Fighting to ignite their season, the Panthers have finally called on Talagi to start in the halves opposite Nathan Cleary for Thursday's match against the Dolphins.

The most-hyped external recruit of the Penrith dynasty has been restricted to only one game from the bench through five rounds so far this season.

Mark Nawaqanitawase is a chance for a late charge into the Roosters' backline after being named 18th player on return from a calf issue.

Former Super Rugby player Tyrone Thompson, brother of Knights prop Leo, will make his NRL debut for the Knights as Jacob Saifiti (calf) drops out of the forward pack.

Jeral Skelton and Jarome Luai respectively return from a hamstring issue and suspension to bolster the Tigers.

Reuben Cotter is back from illness for the Cowboys' clash with Souths.

Jasper Bruce - AAP