The crash happened just before 6 a.m. on Highway 99 near Avenue 18 ½ in Madera County.
The CHP says the brother was driving a pick-up in the southbound lanes when he veered into the center median. The truck then re-entered the roadway and flipped onto its roof.
Officers say the young man and his little sister were not wearing their seatbelts and were both ejected. The siblings died at the scene.
A vehicle described as a dark or red colored SUV or mini-van then hit the 20-year-old's body and did not stop. Investigators are now trying to find that driver.