Hilton, according to Ballard, suffered a setback in practice Wednesday with the same calf injury that caused him to miss three games earlier this month.
"I just can't seem to get a regular injury," Hilton said Tuesday while discussing his ongoing calf issues. "I always get something crazy. It is what it is. I'll deal with it."
Hilton returned from his three-game absence and was on a snap limit against the Houston Texans on Nov. 21. He had three catches for 18 yards in 25 snaps while suffering some tightness in his calf against the Texans.
Hilton entered the season having missed just four games in his career since entering the NFL in 2012. Sunday will be the fifth game that he has missed this season. Hilton leads the Colts in receptions (35), yards (378) and touchdowns (five) this season. The Colts are 1-7 without Hilton in the lineup.
Indianapolis (6-5), losers of three of its past four games, will also be without Eric Ebron, who was placed on injured reserve earlier this week due to an ankle injury.
The Colts could be getting some help back at receiver against the Titans (6-5), as rookie Parris Campbell has practiced twice this week after having surgery on his right hand nearly three weeks ago.
"We've got to see what he can do if he has to wear anything on his hand," coach Frank Reich said. "If he does have to wear something on his hand, can he catch with it? How much protection does he need? I know they have been tweaking and experimenting with some things. We will just see how that goes and how he can practice. I know this, he'll just have to show us that he can do it out there on the field if he has to wear something on the hand."