The accident occurred when a passenger bus, going from capital Islamabad to Karachi, had a head-on collision with a truck in Satharja area of Kahirpur district, police said.
13 people were killed and 15 others injured, a police official said, adding that the rescue team reached the accident site and retrieved bodies from the wreckage of the bus.
An emergency was declared at Khairpur Civil Hospital where doctors confirmed that 13 people had died and 15 others, including women and children, were wounded in the mishap.
Road accidents are common in Pakistan. Most of them are caused by rash driving and bad roads.
Last year, 58 people were killed in a similar road mishap when a bus rammed into a truck in Khairpur district.