The pilotless aircraft struck a compound in the Shahi Khel area of Shawal valley in North Waziristan, one of seven districts near the Afghan border where government forces are battling Taliban insurgents.
A security official said that two missiles were fired which destroyed the compound used by the militants.
“Four militants were killed” and another four injured, he said.
The US often targets rebel hideouts in the tribal region, despite criticism of the unilateral strikes by the Pakistani public and government.
The army has been fighting militants in the district since June. It has killed over 1,500 rebels but they still control parts of the district along the border.