The police on Friday confirmed the attack in the city Gardez, the center of Paktia province.
The assailant exploded the bomb as worshipers were attending Friday prayers.
"Emergency teams have collected 25 bodies from the mosque premises and 40 people have been rushed to hospital," said Abdullah Hazrat, a senior government official who was at the blast site.
Casualty numbers are sketchy. Eyewitness accounts of the bombing put the death toll at up to 30, while another police official said 70 people had lost their lives in the blast, Presstv reported.
No group or individual has claimed responsibility for the attack.
Militants of Taliban and the Daesh Takfiri terrorists in Afghanistan frequently attack civilian and government targets.
Despite the US-led invasion of Afghanistan in 2001, which was conducted as part of Washington’s so-called war on terror, acts of terror remain across the country.
In July, the United States said it was ready to initiate direct talks with Taliban in an attempt to end a 17-year-old war in Afghanistan, a significant shift in American policy in the conflict-ridden country. Taliban have repeatedly declared that they would not enter into talks unless the foreign forces leave the country.