The attack on Monday occurred inside the Shia Muslim Mandinat al-Ilm mosque in the middle-class Gulshan-e-Iqbal area of the port city.
“Four people have been killed, three of them were assailants and one was a policeman,” said Salahuddin Haider, adviser to the provincial minister for information.
“One of them was a suicide bomber who blew himself up. The police reacted after hearing the blast and fired after hearing the blast. As a result two armed people standing outside the mosque were also killed.”
Rizwan Edhi of the Edhi Welfare Trust emergency service said groups of people angered by the blast set fire to a KFC fast food restaurant nearby.
“We are trying to pull out the injured from the mosque as well as those trapped in the KFC,” he said.
A bombing at a Muslim festival in the capital Islamabad a few days ago killed at least 19 people and wounded dozens, mostly Shia Muslims.
Pakistan has been troubled by religious violence since it joined the US-led war on terrorism after the 11 September attacks in 2001.
More than 100 people have been killed in tit-for-tat attacks by majority Sunni and minority Shia groups in the past year.