Locker, who sprained his right hip and knee Sept. 29 in a win over the New York Jets, will return Sunday barring a late setback, the source told ESPN.
NFL.com reported earlier that Locker would start against the Niners.
The Titans (3-3) have lost each of their last two games with Ryan Fitzpatrick as their starting quarterback.
Titans coach Mike Munchak said Friday he was undecided on which quarterback would start against the 49ers.
Locker got a slight majority of the reps in Friday's practice, but Munchak indicated the Titans did more work to make sure Fitzpatrick got the usual amount of reps for a starting quarterback as well.
"We really want to get a feel for what (Locker) feels he can do well and what his limitations may or may not be," Munchak said. "I thought on the field he handled himself really well."
Locker was outstanding prior to suffering the injury three weeks ago, completing 62.2 percent of his passes for 721 yards and six touchdowns with no interceptions over his first four games.
Information from The Associated Press was used in this report.