The accident happened on Route 280 westbound just off the New Jersey Turnpike near Exit 15W in Kearny.
The crash sent the man's vehicle careening sideways and the box truck ran off the road. The victim's identity has not yet been released.
The driver of the box truck remained at the scene and was questioned by police.
The accident caused major delays on the Turnpike during Tuesday's afternoon rush hour, backing up traffic all the way to Route 3.