Hull coach Brett Hodgson has confirmed that Jack Walker and Darnell McIntosh are out for the rest of the season.
Walker, 23, had been on loan at the MKM Stadium from Leeds.
He suffered an early knock in the defeat to St Helens, before recovering to score the first try shortly afterwards inside two minutes.
But he was forced off later on with a foot injury.
McIntosh went off after picking up an injury as he attempted to score a try in the second half of the 60-6 defeat.
Hodgson told BBC Humberside: “They’re both substantial. Jack’s had a syndesmosis injury that I believe requires an operation. Absolutely gutted for the boy, he’s a great kid, he’s just had a baby girl yesterday so it’s bittersweet for him.
“Unfortunately he’s played his last game for us.
“As for Darnell, we don’t know the entire extent at the moment but he’s not going to feature again this season I’d think.”
Hull FC injury woe
Walker and his partner celebrated the birth of a daughter on Wednesday.
He had started six games for Hull, including the wins over Hull KR and Toulouse.
Earlier in the year, Walker had made nine appearances for Leeds. He sat out the whole of the 2021 campaign through injury.
McIntosh arrived at Hull from Huddersfield in the off season. The winger has scored 13 tries in 21 starts.
Hull welcome Wakefield to the MKM Stadium looking to breathe life in to their bid for the play-offs.
They are currently three points adrift of the top six.
Hodgson has called up young academy duo Lewis Martin and Kye Armstrong in to his 21-man squad.
Jake Connor and Kane Evans miss the game through suspension.
Ligi Sao is back after his ban though, while Manu Ma’u is named for the first time since suffering a hamstring injury earlier in the summer.
Hull FC injury woes have left Hodgson without 11 first teamers in total.