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The bomber blew himself up among devotees in the shrine of Sufi saint Lal Shahbaz Qalandar in the town of Sehwan, in Sindh province, police said.
Prime Minister Nawaz Sharif has condemned the attack, which has been claimed by so-called Islamic State.
A surge of attacks this week has shattered a period of improving security in Pakistan,
The shrine was crowded as Thursday is considered a sacred day for Muslims to pray there.
The blast, in one of the country's most revered shrines, is the deadliest in a string of bombings in Pakistan this week, claimed by the Pakistan Taliban and other Islamist militants.
At least 250 others were wounded, a senior police official told the BBC. The only hospital in the area was said to be overwhelmed.
http://www.bbc.co.uk/news/world-asia-38994318