Rose went 9-of-23 from the field, had nine assists and grabbed nine rebounds for the top-seeded Bulls, who claimed a 1-0 lead over the 76ers in their Eastern Conference quarterfinal series.
But the reigning NBA MVP tore a ligament in his left knee near the end of the game and had to be helped off the court.
The team later announced Rose's season was over.
Richard Hamilton added 19 points, while Luol Deng contributed 17 to go with six rebounds for Chicago, which led 52-42 at the half and cruised from there.
Elton Brand finished with 19 points, seven rebounds and four blocked shots for Philadelphia, which managed only 39.8 percent shooting from the field.