The patroness of Santo Stefano Quisquina is Saint Rosalia, celebrated on the Tuesday after the first Sunday of June, with the hermitage dedicated to her on the Quisquina. By episcopal decree of 19 November 2017, Cardinal Francesco Montenegro, metropolitan archbishop of Agrigento, also declared blessed Giacinto Giordano Ansalone secondary patron of the town, known in religion as Giordano da Santo Stefano: born in the town on 1 November 1598, the Dominican friar preached the Gospel in Mexico, the Philippines and Japan, where he was martyred in Nagasaki on 17 November 1634.
The town's mother church, a true jewel of Stefanese sacred architecture, was built around 1580 and adorned with fine stuccowork in the presbytery vault and the marble high altar of 1760, whose altar frontal depicts Christ's five wounds in as many pieces of red marble. Among the town's liturgical feasts, that of Saint Joseph, on 19 March, features the making of the typical altars and the saint's procession through the town's streets.