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A 30-year-old man in the semi-trailer was taken to a Southern California hospital in serious condition, according to Los Angeles firefighters.
The single-engine aircraft The pilot died at the scene, firefighters said.
The plane took off from Torrance, about 20 miles north, with only the pilot on board, officials said. Its destination was not clear.
Onlookers pulled the pilot out of the wreckage and a 911 dispatcher instructed them on administering CPR until first responders arrived, firefighters said.
The National Transportation Safety Board said via Twitter that it was investigating the Piper PA-32 plane crash. The tweet said it was not clear whether an NTSB investigator would visit the site.
The Federal Aviation Administration said it was also investigating the crash.
Media images of the wreckage showed the engine and mutilated front fuselage separated from the rest of the aircraft near a traffic stop.
Firefighters prevented a small amount of fuel on the ground near the plane from spreading further.
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