He became one of the leading Greek composers of his time and is widely regarded as one of the founders of modern Rebetiko and Laiko music.

[5] From a young age, Tsitsanis was interested in music and learned to play violin, mandola and mandolin which were mainstays of so many of his songs.

In 1938, he moved to Thessaloniki, where he completed his military service, and stayed there for about ten years, during the German occupation of Greece.

In 1946, Tsitsanis returned to Athens and began recording many of his own compositions that made famous many of the singers that worked with him, such as Sotiria Bellou (Σωτηρία Μπέλου), Marika Ninou (Μαρίκα Νίνου), Ioanna Georgakopoulou and Prodromos Tsaousakis.

Tsitsanis developed the "westernization" of the rebetiko and made it more known to large sections of the population, setting also the bases for the future laiko.