The flames broke out around 3:30 p.m. on the 2200 block of New Falls Road in Bristol Township.
Firefighters say flames were shooting from the second floor of the two-story building when they got there.
One person was killed, and a second person was treated for smoke inhalation.
Police say the second floor had rooms for rent.
The Red Cross is now helping 12 people who were living there, with a place to stay.
There's no word on what caused the fire.