Justice Minister Nahid al-Rayas told journalists on Saturday the "chaos and unrest" in the Occupied Territories had made his job untenable.
"Unfortunately, the situation is deteriorating by the day."
Al-Rayas said he handed his resignation to Palestinian Authority (PA) Prime Minister Ahmad Quraya on Wednesday, but did not know if it had been accepted.
Senior Palestinian political sources said Planning Minister Nabil Qasis had also resigned after accepting an offer to become president of a West Bank university.
Palestinian areas have been rocked by upheaval in the past few weeks, including kidnappings, street protests and skirmishes between resistance fighters and Palestinain security forces.
The Palestinian leadership is under intense international pressure to clean up corruption and reform its security apparatus, which it accuses Israel of destroying during four years of conflict.
Meanwhile, Israeli occupation forces continue to raid towns in the West Bank and Gaza.
A 16-year-old was shot and killed shortly after military operations begun near the Sufa border crossing in southern Gaza.
Dr Ali Musa, head of Rafah hospital, named the victim as Ahmad al-Qiq.
Troops also arrested four Palestinians from Azbat al-Jarad village near the city of Tulkarm in the West Bank on Saturday morning, Aljazeera's correspondent in Palestine reported.
An Israeli military spokesman said those arrested belonged to the al-Aqsa Martyrs Brigades resistance group.