The fire broke out around 2:15 Monday afternoon near 47th and Orchard Street. Firefighters encountered heavy smoke and flames when they arrived.
Two men inside the house were rushed to the hospital. Mike Marvin lives two doors down and tells Newsradio 1110 KFAB he saw the smoke and flames and ran to the scene. He says he kicked in the front door and broke out some windows.
One of the victims told Marvin the water heater in the basement exploded, but fire officials have not confirmed that.
Marvin says one man suffered serious burns to his face and back and the other had less severe burns on his arms.
The fire did extensive damage to the basement and first floor. Several cats died in the fire.