Illinois State Police responded to the crash in Sangamon County, near Springfield, just after 10:30 a.m.
The crash, which involved multiple cars, happened on southbound Interstate 55 near the Clear Lake exit.
The Sangamon County Coroner's Office said a 14-year-old Chicago girl, a passenger in one of the vehicles, was killed in the crash.
The girl's name was not immediately released.
ISP said southbound I-55 was closed for several hours.
What caused the crash was not immediately clear. The coroner's office and ISP are investigating.
Further information was not immediately available.