Hull's new signings Eldin Jakupovic and Sone Aluko are unlikely to feature.
Swiss goalkeeper Jakupovic, who signed from Greek side Aris, is awaiting international clearance to play, as is Nigeria international Aluko.
Boss Steve Bruce could hand a competitive debut to son Alex after the 27-year-old defender proved his fitness in training this week.
However, the former Sunderland manager is likely to be without left-back Andy Dawson and midfielder Corry Evans with the duo struggling with injuries.
Big-money signing Nick Proschwitz is another player hoping to make his first competitive Hull appearance after moving from German Second Division side Paderborn.
Former Stoke and West Ham defender Abdoulaye Faye should feature.
Rotherham will be without defensive duo Nicky Hunt and Dale Tonge.
New signing Hunt, a free transfer from Preston, will be sidelined for two weeks with a hamstring problem while Tonge also misses out for Steve Evans' side with an Achilles injury.
Midfielder Kari Arnason has been called up for international duty with Iceland but will travel after the game against the Tigers.
Michael O'Connor has been struggling with injuries during the summer but the striker played 90 minutes in the friendly win over Stamford and is in contention to feature.
Alex Revell and Jason Taylor will be fit after picking up knocks against the non-league side.