The four, a woman and three men, were in a saloon car when their vehicle collided with a van at Kaudha centre in Gem.
The matatu is said to have lost control killing the four on the spot and it has not yet been established whether they were family members.
Several people who were in the van were seriously injured after it rolled on impact and were rushed to the Bondo district hospital.
The accident comes almost a month after nine people were killed at Makuyu on the Nyeri-Nairobi highway when a matatu collided with a light truck.
The matatu is said to have been overtaking another vehicle when the accident occurred.