Wolves will be hoping to reach the quarterfinals for the second time in three seasons, while Southampton last reached the final eight in 2017/18.
Nuno Espirito Santo’s men are unbeaten in their last five home matches against Southampton but have kept cleans sheets in just two of their last 17 matches, having beaten Crystal Palace and Chorley 1-0 in the previous rounds to make it to this stage.
Goals are also to be expected in this match as both teams have scored in the last four meetings against each other.
Here’s all you need to know ahead of the game.
The game kicks off at 5.30pm on Thursday 11 February.
The match will be shown live BT Sport 1 and BT Sport Ultimate. BT Sport customers will also be able to stream the game on their mobile devices via the BT Sport app.
Nuno has a number of injury worries coming into this match, with Raul Jimenez, Marcal, Daniel Podence, Willy Boly and Rayan Ait Nouri all set to be out.
Full back Jonny Castro Otto could replace Boly if Wolves switch to a back four, having just returned from a long-term knee injury.
Leander Dendoncker made it into the back three against Leicester and looked at ease, so is likely to feature on Thursday, but his versatility offers Nuno options.
However, Wolves have struggled with scoring goals. Willian Jose is yet to find the net, having started their past three games, but has proved capable of holding onto the ball. This match could provide him with the perfect opportunity to get some goals in.
Hasenhuttl is also without a number of players as Takumi Minamino is cup-tied for Southampton, having already featured for Liverpool in the FA Cup. Also missing will be Alexandre Jankewitz (suspended), Stuart Armstrong, Ibrahima Diallo, Theo Walcott, Michael Obafemi and William Smallbone.
Hasenhuttl could bring Fraser Forster in between the sticks, while Kyle Walker-Peters is likely to return after suffering a quad injury that has ruled him out of the past four matches – which have all ended in defeat.
Mohammed Salisu could also make his long-awaited return, with Hasenhuttl claiming he is the fittest he has been at Southampton.
With Walcott and Minamino out, Dan N’Lundulu could fill the gap in the attack.
Wolves: Ruddy, Semedo, Kilman, Coady, Otto, Moutinho, Dendoncker, Neto, Vitinha, Cutrone, Willian Jose.
Southampton: Forster, Walker-Peters, Salisu, Bednarek, Bertrand, Ward-Prowse, Romeu, Redmond, Djenepo, N’Lundulu, Ings.
Wolves have managed to find a way through the cup so far without playing particularly well and they might take advantage of an under-strength Saints side to do the same again. Wolves 1-0 Southampton.