Officials say that one victim was transported to the hospital and is being treated for burns in serious condition.
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The explosion happened at 1734 22nd Avenue between Noriega and Moraga. The call for the fire came in before 9:30 a.m.
SFFD says that a firefighter has minor injuries and was also transported to a hospital.
MORE: Neighbor describes aftermath of Los Angeles house explosion that was caught on camera
Fire Chief Jeanine Nicholson called the explosion "really, really powerful" and says it completely took the home off its foundation. SKY7 views from the scene show how the house looks imploded, with walls completely collapsed.
She also says it destroyed the house to the left of it, and damaged the house to the right as well. They did a complete search of both houses next door and no one was found inside.
They are not able to search the home that exploded right now, and it is unknown if there were any other people inside.
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Chief Nicholson says that the explosion blew out doors and windows across the street, and car windows up and down the street.
Neighbors said they heard the explosion and felt their houses shake from as far as 20 blocks away.
Evacuations are in place between 1730 and 1750 22nd Ave, and all others on the 1700 block of 22nd Ave are sheltering in place.
Police and fire investigators are on scene working to determine the cause and origin of the explosion.
This is a developing story.