It happened just before 5:30 Friday morning at State Route 152 and Volta Road, near Los Banos.
The CHP says the semi-truck was turning left onto Volta Road when it crossed directly in the path of a man on a Harley Davidson.
The two vehicles collided, and the motorcyclist died on scene.
The driver of the semi-truck was not hurt.
The cause of the crash is under investigation, but officers do not believe drugs or alcohol were involved.