Locker ran for an 11-yard touchdown to put the Titans up 14-0 in the opening minute of the second quarter, but was hit by Browns linebacker Chris Kirksey in the end zone.
"I thought I was clearly in the end zone," Locker said. "I wasn't expecting to get hit. I kind of thought that was a cheap shot."
Kirksey is known for being the "tiny linebacker" in the Madden 15 video game due to a glitch.
Locker was checked for a head injury after the hit but was allowed to return. He went 8-of-11 for 79 yards and a touchdown and ran four times for 34 yards and a touchdown before he was forced to leave with a thumb injury later in the second quarter.
Charlie Whitehurst replaced Locker and threw for 194 yards, two touchdowns and no interceptions in helping Tennessee get out to a 28-3 lead. But the Browns came back to win 29-28 on a last-minute touchdown pass from Brian Hoyer to Travis Benjamin in what was the largest deficit overcome by a road team in a regular season game in NFL history.
Locker was playing in his first game back after missing last week's game against the Indianapolis Colts due to a strained wrist. He also missed 13 games last season due to a Lisfranc injury to his right foot.
In four games this season, Locker has thrown for 764 yards, four touchdowns and four interceptions.
- Ben Estes