Dillon had rushed for 56 yards on 12 carries before aggravating an ankle injury that had forced him to sit out two games earlier this season.
ESPN reported that Dillon was unlikely to return for the second half but Boston College ruled him out for the remainder of the game moments later.
The 6-foot, 245-pound Dillon rushed for 116 yards and two touchdowns on 37 carries last week at Florida State to become the first running back in school history with 1,000-yard seasons as both a freshman and a sophomore.
One of the 10 semifinalists for the Doak Walker Award that goes to the nation's top running back, Dillon entered Saturday's game with 1,052 yards and 10 rushing touchdowns. He has five 100-yard games in 2018, including a season-high 161 yards against Temple on Sept. 29.
As a freshman, Dillon burst on the national scene with 1,432 yards and 14 rushing touchdowns. Dillon capped the season with five consecutive 100-yard games.
That included running roughshod over Syracuse in a 42-14 victory on Nov. 25, when Dillon scored three touchdowns and amassed 193 yards rushing while also nursing an injury.