The basilica has three naves divided by granite columns. At the center of the floor is a disc that covers the well where are collected the remains of martyrs.
The entrance of the church, consisting of a small porch, there is nothing to imagine the extraordinary richness of the interior, where the ninth-century mosaics that cover the apse, the arch apse and the triumphal arch are among the most important in Rome. The triumphal arch leading into the presbytery is decorated with a mosaic depicting the heavenly Jerusalem towards which crowds flock to the Elect; top contained the image of Christ between Angels and Saints, including Santa Praxedes and the sister Pudenziana. The area of the presbytery, the center of which stands a ciborium, is instead decorated with twenty-four Seniors of the Apocalypse which, projecting arms offering crowns to the Mystical Lamb, to the Archangels, to the Evangelists and to the Apostles, symbolically represented here.The apsidal basin presents the Redeemer with Saints Peter, Paul, Praxedes and the sister Pudenziana, Zeno and Pasquale I, who offers a model of the church and is surrounded by a square nimbus instead of round because it was still alive at the time of execution of the mosaics. Lower down, a band with Mystic Lamb at the center with twelve sheep, symbolizing the apostles, the two sacred rivers the two holy cities, Jerusalem and Bethlehem.
Half of the right aisle is the Chapel San Zeno, built by Pope Pasquale I as a mausoleum of the mother Theodora. It 's nicknamed the Garden of Paradise, for its Byzantine-style mosaics.
In a niche, opened in the Chapel of St. Zeno is kept a column about 63 cm high, traditionally considered the pillar of the scourging of Christ.