Firefighters responded before 1 p.m. to the home near Adams and West avenues, just outside of Easton.
Investigators were going through the home, trying to piece together what happened.
A neighbor told Action News that the homeowner's dog tried to pull her into the home, likely to help save the man.
Rose Rodriguez says she tried to get inside when the German Shepherd tugged at her, pulling her to the side of the home.
By the time fire crews arrived, they say flames were shooting out of all four sides of this home. Despite hearing ammunition firing off in the home, firefighters still went inside to try and save the man trapped in his home.
"I heard that there was a disabled man -- 67 years old, cancer, bedridden, unable to get out of the home," said Rodriguez. "We tried to get into the home to see if we could help; wasn't able to get very far into the home. It went up pretty fast."
"The cause and origin will be determined here in the next few hours. Crews will remain on scene. There was a lot of contents and structure destroyed on the back half of the building," said Cal Fire Capt. Ryan Michael.
Fire crews say it appears the flames first took off in the back of the home.
The Fresno County Sheriff's Department Crime Scene Unit also responded to the scene, which authorities say is a standard procedure for a deadly house fire.
Action News was told that the family had four dogs -- two of them died in the fire -- and we spotted deputies watching over the surviving dogs.
The man killed in the fire has not been identified.