The crash happened around 8:50 a.m. under the Spruce Street overpass.
Among the vehicles involved were a tanker truck and a box truck.
There was no immediate word on the identity of the person who was killed.
The southbound lanes were shut down for nearly two hours, with the highway finally reopened around 11:00 a.m.
The view from Chopper 6 HD showed a massive backlog on the highway.
The circumstances of this crash remain under investigation.