The early 12th century brought the crusaders to Syria and Palestine. Saffuriyya (Sepphoris) became one of their local bases, they called it Le Sephorie.

The Crusaders rebuilt the  Byzantine citadel atop the hill,  overlooking Saffuriyya (Sepphoris), they rebuilt also the Byzantine Church and dedicated it to Anne and Joachim, the parents of the Virgin Mary. They built al-Quastal fortress to defend the water spring.

In 1187, the Crusaders were dispatched from Saffuriyya (Sepphoris) to fight against Saladin in Hattin,. They were defeated at Hattin, and the Third Crusade ultimately failed as a whole. Muslims entered Saffuriyya (Sepphoris).  

By mid-September, Saladin had taken Acre, Nablus, Jaffa, Toron, Sidon, Beirut and Ascalon, and Jerusalem fell to the Muslim army on October 2, 1187.

In 1263, Zahir Bibars entered Saffuriyya (Sepphoris), definitive depart of Crusaders.