The settlers entered the old city of al-Khalil on board 120 buses early on Friday, and broke into the mosque courtyard amid protection by Israeli troopers, Hebrew-language Maariv daily reported.
Israeli forces deployed several military vehicles around the Ibrahimi Mosque, also called the Cave of the Patriarchs.
On February 25, 1994, at least 29 Palestinians were killed and 125 others wounded when American-Israeli Baruch Goldstein opened fire on a large number of Palestinian Muslims, who had gathered inside the Ibrahimi Mosque to say dawn prayers during the holy fasting month of Ramadan.
The occupied Palestinian territories have been the scene of heightened tensions since August 2015, when Israel imposed restrictions on the entry of Palestinian worshipers into the al-Aqsa Mosque compound in East Jerusalem al-Quds.
Palestinians are angry at increasing violence by Israeli settlers at the al-Aqsa Mosque compound, saying the Tel Aviv regime seeks to change the status quo of the sacred site.
More than 220 Palestinians have lost their lives at the hands of Israeli forces since the beginning of last October.