Police said a man was inside a home in the Back of the Yards neighborhood's 4700-block of South Damen Avenue when a fire broke out just after 3:15 p.m.
The man, whose age was not immediately known, was taken to Stroger Hospital, where he was pronounced dead.
His identity was not immediately released.
How the fire started was not immediately clear.
Area detectives are investigating.
Authorities did not immediately provide further information.