The roof of a central Shia Muslim Imambargah came down after an explosion in Lakhi Dar area of Shikarpur, around 470 kilometres north of here, when people had assembled for the Friday prayers.
"It was a big explosion inside the Imambargah and was set off with a remote device. The intensity of the blast led to the roof of the make-shift building caving in completely which has led to many deaths," senior police official Abdullah Mehr said over telephone.
Private media said it could be suicide bombing.
Dr Shaukat Ali of District Civil Hospital said 20 people were killed in the attack during the Friday prayers.
Around 50 others were injured.
SSP Shikarpur Saqib Ismail Memon told reporters that a large number of victims have been taken out from under the debris.
Several injured were said to be in a critical condition.
Mehr said there was chaos at the site of the blast as the number of people injured were high and they were being shifted to nearby hospitals.
But local provincial lawmaker Shehyar Mehr said hospitals in the area did not have the required staff or equipment to deal with such a big emergency.
"From what we are being told, at least 30 people have already died in this tragic incident and the numbers could rise," he said.
The blast is the latest in a rising tide of sectarian violence blighting Pakistan.
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