It happened at about 1:50 a.m. at the Wood Street crossing at 147th Street, according to CSX.
Four young women were inside the car when it was struck by an oncoming train, according to Harvey Fire Department Captain Steve Gorman.
The details of the crash are not yet known but firefighters were forced to extricate two of the victims from the vehicle using the jaws of life.
Three of the women were transported to area hospitals and one refused treatment, Gorman said.
At least one of the victims is listed in critical condition at Advocate Christ Hospital in Oak Lawn.
The Dixmoor Police Department assisted with the crash.
A cause of the crash is under investigation.