The attack came as a group of Shiites were holding a meeting to settle a land ownership dispute in a village in Orakzai tribal district.
Orakzai is one of Pakistan's seven lawless tribal districts on the Afghan border considered to be the hub of Taliban and Al-Qaeda linked militants.
"Three attackers came in a jeep and hurled four grenades on the participants of the meeting," senior administration official Mehmood Aslam told AFP.
"Four people were killed and two others were injured. The guards of the participants fired back and killed one of the attackers," he said.
Anti-Shia violence is on rise in Pakistan, with Taliban and Lashkar-e-Jhangvi militant groups regularly attacking Shiite gatherings.