The crash occurred at about 2:23 a.m. in the outbound lanes of I-290 near Pulaski Road.
Police said the pedestrian was transported to Mt. Sinai with critical injuries.
Police said the pedestrian was struck by a vehicle which spun out and struck another vehicle.
It is unclear why the pedestrian was in the roadway.
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The outbound lanes of I-290 were closed between Independence and Cicero before re-opening around 6:30 a.m.