Hull captain Ian Ashbee faces a spell on the sidelines after scans revealed the midfielder has ruptured his posterior cruciate ligament.
Ashbee was injured in the early stages of Monday's Premier League defeat at Aston Villa in a collision with James Milner.
The club are unsure how long the 32-year-old will be out but his season is almost certainly over.
Manager Phil Brown told the club's website: "Ian is going to be out for a number of weeks with the injury.
"However, further investigation is still required. We can't actually go in to have a look because of the wound that is on his knee at the moment.
"But the results of the scan say that he has got a ruptured PCL. We'll have further information when we can put a scope in there and find out a little bit more, but we won't be able to do that for another seven days."
Ashbee, who has played in all four divisions since joining Hull in 2002, missed more than a year of action from 2005-06 due to a serious knee injury and bone disease.
He is the second Hull player to suffer a knee injury this season after record signing Jimmy Bullard underwent a major operation earlier this year.