Fire crews responded to the home on N. Cherokee Avenue, between De Longpre and Fountain avenues, around 3 a.m.
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According to the Los Angeles Fire Department, firefighters had to rescue two men who were trapped behind a metal door inside the home.
The door was apparently double locked, forcing firefighters to use a saw to get through. The men were rushed to the hospital, one of whom was last listed to be in grave condition.
"I heard like little pops crackling, almost like popcorn, and that's what had woken me up," said a neighbor named Sebastian. "I went outside and I seen little bursts of flames coming out the windows. It was empty. No one was here and I heard yelling up in the front. I guess it was people trying to get the homeowner and whoever was living with him out of the house because they were stuck. He couldn't open the metal gate."
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Investigators said a flashover occurred when fire crews were inside the home and one firefighter sustained ear burns.
The cause of the fire remains under investigation.