Karachi Commissioner Shoaib Siddiqui said the accident took place on the Super Highway when the bus going from Karachi to Shikarpur collided with the oil tanker early today.
"It was the mistake on part of drivers of both vehicles as they were over speeding and the passenger bus was overloaded with some passengers even sitting on the roof," Siddiqui told PTI.
According to Jinnah Post Graduate Medical Centre (JPMC) emergency department incharge Seemi Jamali, 57 bodies including women and four injured have been shifted to Jinnah Hospital, where emergency has been declared.
One survivor told Geo News channel that the passenger bus was overcrowded and the driver was also over speeding.
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"He lost control and panicked when the oil tanker driver lost control and came the wrong way," he said.
Television channels showed both vehicles on fire as rescue workers and fire engines went about their work.
Road in the Sindh province are notorious for being poorly maintained while lax checking by the highway police also emboldens drivers to over speed during night time.
In March, 43 people were killed when an oil tanker crashed into a trailer tractor on the highway.
Close to 9,000 road accidents are reported to the police every year since 2011, killing over 4,500 people on average, according to the Pakistan Bureau of Statistics (PBS).