The altar of the Holy Family of Joseph, Mary and Jesus is a beautiful work of art decorated with inlaid precious marble and a canvas painted by Maltese artist Giuseppe Calì in 1899. This altar, formerly dedicated to the Most Holy Trinity, used to be associated with the Trinitarian Confraternity, a Medieval association of laymen who strove for the redemption of Christian slaves.

In the year 2000 of the Great Jubilee, an authentic icon of the Incarnation of Our Lord was sent to this basilica by the Ecumenical Patriarch of Constantinople as a sign of Christian unity, and is now venerated on this altar.