It happened about 11:30 p.m. at West Jackson Boulevard and South Kilbourn Avenue in the Garfield Park neighborhood.
Chicago fire said when they arrived, smoke was pouring from the building's basement.
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A woman in her 70s who was pulled from the home was taken to Mount Sinai Hospital in critical condition for smoke inhalation.
Fire officials said a man in his 60s was found dead inside the home.
This is a developing story; check back with ABC 7 Chicago for updates.