The early Tuesday morning accident killed 21 people, including five children and two babies. A further 39 people were injured.
The bus, en route to the southern city of Asyut, collided with the van, flipped over and burst into flames, incinerating most of the passengers, a police source told AFP.
The accident, in the southern governorate of Minya occurred when the driver of the bus fell asleep behind the wheel, police said.
Five children, including two babies were among the victims. The injured, some in serious condition, were taken to hospital, the source added.
Fatal road accidents are common in Egypt, where many drivers do not abide by the highway code.