The bomb went off on the busy Maka al Mukaram road on Sunday, police said, while a witness said the blast was followed by big clouds of smoke visible in sky.
"So far we know six civilians died and 20 others were injured. They were mostly pedestrians while others were shopping," the police officer said.
"Death toll may rise. Most of the injured ones are very serious," said Major Mohamed Hussein, a police officer.
Earlier, a Reuters reporter at the scene of the blast had counted four bodies lying on the ground. Photographs showed three destroyed cars on the road, with two still burning.
It was not clear who was responsible for the blast.