The Church, situated on the Esquiline hill between the two basilicas of St. Mary Major and St. John Lateran, is one of the rare examples of neo-gothic architecture in Rome. Although dedicated to the Most Holy Redeemer, it was built in honor of Saint Alphonsus Liguori, the founder of the Redemptorist Congregation, and thus bears his name.

It was built in 1855-59, according to the plans of the Scottish architect, George Wigley, on the grounds of the ancient Roman Villa Caserta, a property acquired by the Redemptorists from the Caetani family. The church measures 42x14 meters and was consecrated in 1859 by the Cardinal Costantino Patrizi. Tradition tells that, while excavating the foundations of the church, there was found a gold coin bearing the effigy of the Redeemer, this being seen as a good omen.

Three doors in gothic style lead to the vestibule of the church. The tympanum over the central door is decorated with a beautiful polychrome mosaic of Our Lady of Perpetual Help. Over the tympana of the side doors are two bas-reliefs on gold mosaic backgrounds, by Antonio della Bitta, depicting on the left Saint Alphonsus and on the right the Redemptorist saint, Clement Hofbauer. On the apex of the arch above the central door stands a statue, in carrara marble, of the Holy Redeemer. High above this is a magnificent rose window in honor of Our Mother of Perpetual Help, flanked by two small circular windows. Above the rose window is a Latin inscription bearing the motto of the Redemptorist Congregation:  "For With Him there is Plentiful Redemption".  The pediment supports a Celtic cross, restored in 1964.

One enters the church by ascending a flight of 24 wide steps, constructed in 1932. Inside, columns of colored marble separate the large central nave from two side aisles. One will note that the architect, Wigley, did not exactly follow the rules of Transalpine gothic, but was seeking a modern interpretation. The nave, separated from the side aisles by wide transversal arches, typical of the neo-gothic of Southern Italy, presents a rich spectacle of polychrome marble. The side aisles contain six small chapels, erected between 1932 and 1939, dedicated to St. Theresa of Avila, St. Joseph, The Holy Family, St, Francis of Assisi, Our Lady Immaculate and St. Alphonsus. The confessionals, constructed at the beginning of the twentieth century in florid gothic, following the design of Gerard Knockaert, are the work of the Redemptorist Brother, Gerardo Uriati, a noted cabinet maker.

The stained glass of the rose window and that of the windows in the side aisles is of French origin and the work of the Dominican Brother, Marcellino Leforestier. During the years 1898-1900, two Redemptorists, the Belgian architect Gerard Knockaert (1845-1928) and the Bavarian painter, Maximilien Schmalzl (1850-1930) dedicated themselves to the embellishment of the church and to maximizing its available space. The paintings in the chapels and on the arches of the central nave, the work of Schmalzl, all date from this time, as well as those on the gallery, above the side aisles, which opens on to the nave through a series of three-mullioned windows.

At the end of the nave, on the triumphal arch above the entrance to the sanctuary, one is struck by the early twentieth century painting, by Eugenio Cisterna, depicting the Coronation of the Virgin with the Angels and Saints of the Redemptorist Congregation. Underneath is the inscription in Latin telling "The Holy Mother is exalted above the choirs of angels to the heavenly kingdom". Cisterna is also responsible for the painted medallions of Apostles and Saints to be found above the arches of the side aisles. On the arch of the apse there is another Latin inscription: "You have redeemed us by thy blood and have made us a kingdom to our God". High above the sanctuary there is a large painted Cross on a gold background flanked by the coats-of-arms of Pope Paul VI and the late Cardinal Joseph Ritter of Saint Louis, U.S.A.

The splendid mosaic in the apse, depicting the Redeemer enthroned between the adoring Virgin and St. Joseph, was created in 1964 and superimposed on an earlier fresco by Rodhen.

In 1995 the icon of Our Lady of Perpetual Help was restored to its original form.  All later additions to the original icon such as crowns containing precious stones were removed.  The sanctuary of the Church was renewed during the same period changing the setting for the original icon to the one presently seen.