Locker picked up a foot injury late in the first half of his side's 29-27 defeat to the previously winless Jacksonville Jaguars yesterday, continuing for another play before being replaced by Ryan Fitzpatrick.
The 25-year-old suffered a suspected Lisfranc injury on an eight-yard run and could require surgery, according to The Tennessean.
Locker admitted that he was not sure how the injury occurred but revealed that he knew something was wrong after the play.
"I really don't know how it happened. Just when I got up I could feel it," Locker told reporters.
Fitzpatrick has already filled in for Locker this season, having played twice while the first-choice quarterback was out with a hip and knee injury earlier in the campaign.