The incident occurred at about 11:15 p.m. in the outbound lanes of I-290 near Independence Boulevard.
Police said the 61-year-old woman was transported to Stroger Hospital in critical condition. It is not known what she was doing on the expressway.
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All outbound lanes of the expressway were closed at Independence before reopening shortly after 4:30 a.m.
The driver of the vehicle stopped at the scene and is cooperating with police, ISP said.