Higgins was taken to the locker room in the first quarter with an apparent injury.
The star pass-catcher was banged up after attempting to make a catch along the sideline. He was taken to the medical tent to be evaluated before leaving for the locker room.
The junior receiver was the Tigers' top wideout this season, recording 1,082 yards and 13 touchdowns on 52 catches.
Higgins exploded for 182 yards and three touchdowns in Clemson's 62-17 win over Virginia in the ACC Championship game on Dec. 7.