Local news media report the plane crashed into the house in San Diego's Clairemont neighborhood about 4:40 p.m. Saturday.
The single-engine, six-seat Beech BE36 Bonanza had taken off from Montgomery Field about a half mile away.
The San Diego Union-Tribune reports the pilot and a passenger were taken to a hospital with burns, and two passengers died at the scene.
The paper reports the pilot apparently tried to land in a field behind the house. The plane skidded through a fence and crashed into the back of a home, sparking a fire.
The occupants of the house were not home, but neighbors said their small dog died.