It happened just before 5:30 am Monday on Highway 190 at Road 208, west of Porterville.
Officers say a 2020 International semi-truck hauling two trailers was heading west on Highway 190 when the driver of a GMC heading south on Road 208 went through a stop sign.
The GMC hit the right side of a trailer as the truck passed the intersection.
The 49-year-old man from Strathmore driving the G-M-C was pronounced dead at the scene.
His two passengers were also hurt and taken to Kaweah Health.