The deadly accident occurred in the early hours on the Super Highway about 50 kms from here in Sindh province as the bus was travelling from Karachi to Shikarpur, Karachi Commissioner Shoaib Siddiqui said.
The overcrowded bus, carrying around 80 people with some sitting on its roof, collided with an oil tanker coming from the opposite direction and wrong side of the road.
The driver of the tanker is absconding.
"It was a very tragic incident because those killed include women and children and most were burnt alive after the bus and tanker caught fire," Siddiqui said.
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He said rescue workers recovered bodies of children stuck to their mothers as they were apparently trapped after the collision and could not escape the fire.
The devastating incident also killed nine members of a Karachi family, including its 80-year-old head and a two-year- old toddler.
Seemi Jamali, the emergency department incharge at the hospital, said most of the bodies were beyond recognition and could only be identified with DNA tests.
An unspecified number of injured have also been shifted to the Jinnah Hospital, where emergency has been declared.
"The death toll has climbed since this morning as rescue workers recovered bodies from the burnt vehicles after the fire was put off," she said.