E. De Felice notes that this surname derives from the name Siro, which in the Liguria area has an old tradition linked to the cult of two saints of the 4th century with that name: one bishop of Pavia and another of Genoa, to whom the church of San Siro di Struppa and the old cathedral of the centre of that city are dedicated. According to De Felice, Siro continues the Latin cognomen of ethnic origin Syrus, which meant "inhabitant or native of Syria," frequent as a name of slaves and freedmen and later extended in Christian circles.

E. Rossoni adds that the surname may also derive from the Latin indirect form Sirone (Siro, Sironis), illustrated by the celebrated Epicurean philosopher whose school in Naples had among its disciples Virgil. Rossoni specifies the geographic distribution: Siri is typical of central-western Liguria, while Siro, very infrequent, also belongs to that region. Sirone, practically rare, would seem to originate in the Agrigento area. Sironi, on the other hand, is typical of Lombardy and would derive from the place name Sirone, in the Lecco area, with an additional presence in the Genoa area and in the Reggio Emilia area.