Best was left out of Newcastle's 22-man match squad entirely on Tuesday before it was revealed late last night that he would require surgery later this week to repair a ligament in his right thumb.

It is another crushing blow for the 20-year-old centre, who only returned from a five-week injury layoff against Souths on Friday, scoring a try in the 40-28 loss.

Best has had a string of injuries in recent years and missed four games after dislocating an elbow against the Broncos in May.

He required surgery on his left thumb last year and wore a boxing glove during the preseason in order to train.

He is expected to be out for at least a couple of weeks following surgery on Friday.

He is a huge out for the 12th-placed Knights who will be trying to keep their slim finals hopes alive with a win at Brookvale on Saturday.

Best will be replaced by Dane Gagai should the Queensland representative get through Origin III unscathed on Wednesday.

Gagai and Maroons teammate Kalyn Ponga, along with NSW prop Jacob Saifiti, will have their fitness assessed upon return from the Origin decider but have been named to play for Newcastle.

Back-rower Brodie Jones returns to the side and is on the bench with Saifiti, Simi Sasagi and Pasami Saulo.

Chris Randall, Mat Croker and Leo Thompson have dropped out of the 17.

Hooker Jayden Brailey will start the game and says he is ready to play a more dominant role. The club captain returned from his extended injury layoff via the bench against Souths, replacing Chris Randall at halftime.

Brailey said on Tuesday while he pulled up "a bit sore" from his 40-minute spell, he was ready to embrace the physicality of starting the game this week.

"I was sore from the contact but the Achilles and everything else was fine," he said. "Randy has done a really good job this year.

"He has probably been our most consistent player and has really helped me transition back into the team.

"I get a chance to start again this week. I'm really looking forward to it. I felt like I was able to get back in my rhythm last week and it's something to build on."

Apart from Bradman Best, Knights coach Adam O'Brien had almost every player in the club's top-30 roster available to select this week.

Prior to having a bye last week, Manly beat Melbourne 36-30 and let a victory go begging when they lost 28-26 to North Queensland.

Running eighth, six points ahead of Newcastle, the Sea Eagles have had eight wins and eight losses this season.

They beat the Knights 30-6 in round five but Newcastle were in the contest up until about the 70th minute.

Sea Eagles stars Daly Cherry-Evans and Jake Trbojevic have been named to back up from Origin.

Meanwhile Novocastrian Zac Hosking, who debuted for Brisbane on Sunday, has been retained to face the Gold Coast on Saturday.

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