The fire broke out about 1:30 Friday morning in a house along the 1400 block of West Girard Avenue near Broad Street.
Firefighters had to battle through smoke and flames to reach the victim who was trapped inside the house.
He was treated at the scene for smoke inhalation, then rushed to the hospital without any vital signs.
He was pronounced dead at the hospital.
Five other people in the house managed to get out safely. The Red Cross is finding temporary housing for them.
Investigators are looking for the cause.