Outscored 11-1 in their current rut, Hull have slipped to 20th in the standings after being as high as third at one point while Luton sit 11th following a 2-0 win over Blackburn Rovers.
Luton have won three on the trot against Hull dating back to September of 2019.
Shota Arveladze was sacked on Friday morning after just eight months in charge. The club statement confirmed that assistant head coach Peter van der Veen also left the club, with Andy Dawson taking over the role of interim head coach.
Arveladze had stated that Dogukan Sinik could make his debut for the Tigers after signing for the club in July. The Turk has been sidelined with a calf injury, but returned to full training this week.
Harvey Vale picked up a groin injury with the England U-20's and is set to miss out while Salah Eddine Ouland M'Hand remains sidelined.
Alfie Doughty is in line to make his debut for the Hatters. The former Stoke City man was a substitute against Blackburn two weeks ago, but has yet to feature due to injury.
Harry Cornick missed out on the victory over Blackburn Rovers with a groin injury while the availability of Amari'i Bell is up in the air after traveling to the United States for Jamaica's friendly against Argentina.
Hull City: Baxter; Elder, Greaves, McLoughlin, Coyle; Slater, Seri; Longman, Tufan, Vale; Estupiñán
Luton Town: Horvath; Potts, Lockyer, Burke; Bell, Campbell, Clark, Freeman, Bree; Woodrow, Morris
Oscar Estupinan (Hull City)
While he has only scored in three appearances, Estupinan has made them count, having found the back of the net seven times to lead the Tigers attack, proving to be a sensational acquisition.
Carlton Morris (Luton Town)
The Hatters' number nine has been in a rich vein of form recently, scoring twice in the draw with bottom club Coventry City and following it up with the match-winner against Blackburn.
Where is the match being played?
The action will take place at the MKM Stadium.
What time is kick-off?
The match is scheduled to begin at 20:00 BST.
How can I watch the game?
Sky Sports Football will provide the coverage, which will begin a half-hour before kick-off at 19:30 BST.