The home is at Lyon Street and Clay Street, and officials say heavy fire was coming from all four floors.
SFFD says no one was at the home at the time of the fire, which has since been put out. They also say smoke conditions have "improved considerably."
There is scaffolding on the building, which appears to have been getting renovated.
It is unclear the extent of the damage, but several parts of the home appear to be totally destroyed.
It's also unclear what caused the fire.
Stay with ABC7 News for updates on this developing story.