The settlers broke into al-Salam Mosque, ransacked its contents and blocked roads leading to the town's junction, according to witnesses.
The incident is part of escalating settler attacks targeting Palestinian properties and religious sites in the Salfit area.
Separately, the Palestinian Ministry of Awqaf and Religious Affairs condemned the intrusion.
In a statement, the ministry described the act as desecration of the site and an affront to Muslim places of worship.
Meanwhile, Israeli forces raided the Jalazun refugee camp north of Ramallah.
Troops entered the camp and opened fire with live ammunition toward Palestinians, sources said.
Israeli forces stormed the town of Ni'lin west of Ramallah.
Local reports indicated soldiers fired tear gas canisters at residents, sparking clashes.
Clashes also erupted during an Israeli raid on the town of Silwad northeast of Ramallah on Friday evening.
Youths confronted troops, leading to confrontations, according to local sources.
In another incident, settlers attacked the Briq area in the northern Jordan Valley.
The Palestinian Red Crescent reported one Palestinian injured in the assault.
Meanwhile, local sources reported settler incursions into villages including Atara north of Ramallah, where a settler grazed livestock on Palestinian land in a provocative act.
In another development, forces raided the village of Burin south of Nablus, triggering clashes with local youths.
Zionist troops also targeted the town of Burqa northwest of Nablus.