It happened at 2:30 p.m. Friday on northbound I-295 at Arena Drive in Hamilton Township.
New Jersey State Police say a flatbed truck carrying drywall collided with a Lexus.
Images from Chopper 6 HD over the scene showed the truck on its side and the Lexus heavily damaged.
Both were in the grassy median separating the north- and southbound sides of the interstate.
Police say one person was trapped in the wreckage.
It was not immediately clear whether the fatality occurred in the Lexus or the truck.
The two left lanes of northbound 295 were blocked and two other lanes getting by as crews worked to clear the scene.