By tradition, this church was built to mark the spot where Pope Saint Sixtus II (257-258), on his way to martyrdom, met Saint Lawrence during the Valerian persecution (253-260) towards the end of the Roman Empire. Its original name was the titulus Tigridae, possibly the name of the Roman lady on whose property it was built. The first recorded mention of it was in 595 at the Council of Rome. The Dialogues of St. Gregory the Great mention the nomination of the priest Basso to the title of St. Sixtus, and St. Gregory chose the church as one of the Lenten stations.
The church was restored in the eighth and ninth centuries, and Gregory IV (827-844) presented the church with sacred vestments. After that it seems to have been neglected, since Innocent III (1198-1216) had to rebuild it almost completely. In 1219 Honorius III (1216-1227) entrusted the church and monastery to the recently-founded Dominicans, and St. Dominic (1170-1221) himself lived for some time in the monastery, collecting there about a hundred friars before he was given Santa Sabina on the Aventine.
Sixtus IV (1471-1484) ordered the complete renovation of the ceiling and the rebuilding of the façade, and its doorway is now in the southern wall. In the 16th century Filippo Cardinal Boncompagni, its titular, carried out extensive renovations. About the same time, the Dominican nuns living in the convent attached to the church received permission to vacate it on account of the malaria raging in the district. In the 18th century Pope Benedict XIII (1724-1730), a Dominican, planned a restoration for the church. This plan, however, was abandoned in the midst of the invasion of Napoleon until 1856 when the Irish Dominicans, who had charge of the church from 1677-1798, restored it.
In the 6th century the relics of Pope St. Sixtus II were translated from the Catacombs of St. Callistus to this church. Its Romanesque bell-tower dates from the 13th century, and inside the church is an interesting 13th century fresco cycle depicting Scenes from the New Testament and the Apocrypha. ~From Pontifical North American College, Station Churches of Rome