The veteran forward, who scored the opening goal for Steven Gerrard's side, crumpled to the turf as he chased a ball behind the Staggies' defence.
He received treatment on the pitch, but was replaced byu Joe Aribo when it became clear the former England internationalist would be unable to continue.
Rangers' official Twitter account tweeted: "Jermain Defoe is unable to continue and is stretched off the pitch to a standing ovation at Ibrox."
Alfredo Morelos was named on the bench after overcoming his own injury scare, but with Defoe possibly facing a lengthy spell on the sidelines, it appears Gerrard was unwilling to risk further injury to the Colombian hitman, with fellow striker Greg Stewart also unavailable through injury.
Morelos eventually entered the fray replacing winger Ryan Kent on 68 minutes but Gerrard's injury worries are mounting up ahead of Saturday's home match against Aberdeen and the midweek trip to Hibs on 5 February.
Rangers could be without up to five first-team players with defenders Filip Helander and James Tavernier out - with the latter expected to be sidelined for a further fortnight - while midfielder Ryan Jack as well as Stewart and Defoe could miss one or both games as well.