ISP said the crash happened on I-80 westbound between La Grange Road and Harlem Avenue in Tinley Park just before 4:30 a.m.
The crash involved an SUV and a semi, ISP said. What led up to the collision was not immediately clear.
Two people were pronounced dead.
All westbound lanes were closed at the scene, and the Harlem Avenue ramp was also shut down. All lanes have since reopened.
ISP did not immediately provide further information about the crash.