South Sydney Rabbitohs prop Mark Nicholls will be facing some weeks on the sideline after suffering a syndesmosis injury during Friday evening's clash against grand final nemesis, the Penrith Panthers.

Nicholls would last just 60 seconds in the match, being injured on Penrith's first touch of the night as he attempted to be involved in a four-man tackle.

Penrith fullback Dylan Edwards, bringing the ball back off his own line, ran into Nicholls, Cody Walker and Cameron Murray, before Tevita Tatola also entered the tackle over the top.

Nicholls had his right ankle dig into the turf and turn outwards during the tackle, with concerns expressed for both the knee and ankle originally before South Sydney's medical staff confirmed the injury.

Pictured with his foot and ankle in a bucket of ice on the sideline, Fox Sports sideline reporter James Hooper confirmed he was done for the evening with a syndesmosis problem.

Scans will be required over the weekend to confirm the extent of Nicholls' injury, with syndesmosis injuries generally ruling players out for anywhere between four and ten weeks, pending on the grade and injury type, as well as whether surgery is required.

Nicholls, who will join the Dolphins in 2023, has been a consistent force for South Sydney over the past two years, playing in last year's grand final.

He was replaced immediately by Jacob Host, with South Sydney forced to play the game with just 16 players.

Penrith were leading 20 points to 6 with a little over 25 minutes remaining in the game.