He was made a referendary prelate of the Supreme Tribunal of the Apostolic Signature in 1870, and accompanied Archbishop Alessandro Franchi to Constantinople in 1874, the same year in which he was named Secretary for Oriental Affairs in the Sacred Congregation for the Propagation of the Faith.

On 22 May 1877 Aloisi Masella was appointed Titular Archbishop of Neocaesarea in Ponto by Pope Pius IX.

Pope Leo XIII created him Cardinal Priest of S. Tommaso in Parione in the consistory of 14 March 1887.

He was appointed Prefect of the S.C. of Rites on 3 October 1889, and also served as Camerlengo of the Sacred College of Cardinals from 11 July 1892 to 16 January 1893.

He opted for the titular church of S. Prassede on 16 January 1893, and was named Pro-Datary of His Holiness on 29 May 1897, remaining in that post until his death.