The Cavaliers were within four points with 7 minutes to play when Philadelphia put together a 10-2 spurt.
The only two 3-pointers Holiday hit in the game came during that stretch, which led to the 76ers winning their second in a row.
Evan Turner scored 23 points and grabbed 13 rebounds for Philadelphia, which is in ninth place in the Eastern Conference playoff race with little chance of catching eighth-place Milwaukee.
Holiday finished with 18 points and Thaddeus Young contributed 16 for the 76ers.
C.J. Miles came off the bench to deliver 19 points for Cleveland, which has lost seven in a row.