The crash happened around 2:40 pm on the southbound lane of Highway 99 near Avenue 24 in Earlimart.
The California Highway Patrol says the big rig, which had two attached trailers carrying wooden pallets, overturned and landed on its roof, then caught on fire.
Fire crews were working to put out the flames.
At least one person inside the big rig was killed in the crash.
CHP officers say they do not yet know if there was more than one person inside.
A portion of southbound Highway 99 is closed and traffic is being diverted off Avenue 24.
Traffic is backed up on the highway for several miles.
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