It happened around 12:15 Saturday morning on the Route 52 bus near the intersection of 54th Street and Springfield Avenue.
Authorities are not sure what sparked the stabbing but say the man was stabbed in the face.
He was taken to the Hospital of the University of Pennsylvania - no word on his condition.
A SEPTA spokesperson told Action News that surveillance video from the bus was provided to police.
Philadelphia and SEPTA police are investigating.