A woman has been killed after a stationary car she was sitting in was struck by a light plane on a highway in California.

The single-engine plane landed in the slow lane of Interstate 15 near San Diego just after 9:15am local time on Saturday, then slid to the shoulder before hitting the vehicle.

The 38-year-old woman was pronounced dead at the scene.

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The 60-year-old pilot sustained life-threatening injuries to his head, and his passenger along with three passengers in the car — two men and a woman — were taken to hospital for treatment with less serious injuries, according to local news reports.

John Marshall, who was on his way to work when the crash happened about 90 metres in front of him, told ABC News the plane's engine was not running and the landing gear was not down when it made impact.

"He came in gliding right over the top of me," Mr Marshall said.

"It was a good landing, unfortunately the guy in the car was at the wrong place at the wrong time."

Mr Marshall along with a number of other witnesses rushed to the aid of the passengers, but he said his greatest concern was originally for the pilot.

"The people in the car, they were moving around, I originally thought they were OK," he said.

"The plane was spewing fluid, spewing gasoline, and the pilot, he was leaning over the stick there, slumped down so he looked in the worst shape."

Mr Marshall said it took emergency services about 10 to 15 minutes to arrive on the scene at which point they realised the woman in the back was critically injured.

The car had reportedly pulled over to the side of the road while the occupants tried to sync the bluetooth system.

"They did everything right, they pulled over and stopped," an emergency worker told local news crews.

The National Transportation Safety Board said it was investigating the crash but could not determine the cause at this stage.