Italian broadcaster RAI announced in October 2020 that the winning performer(s) of the Sanremo Music Festival 2021, later turning out to be Måneskin with "Zitti e buoni", would earn the right to represent the nation at the Eurovision Song Contest in Rotterdam, the Netherlands.

Since 2015, the winning artist of the Sanremo Music Festival is rewarded with the opportunity to represent Italy at the Eurovision Song Contest, although in 2016 the winner declined and the broadcaster appointed the runner-up as the Italian entrant.

Italian broadcaster RAI confirmed that the performer that would represent Italy at the 2021 Eurovision Song Contest would be selected from the competing artists at the Sanremo Music Festival 2021.

According to the rules of Sanremo 2021, the winner of the festival earns the right to represent Italy at the Eurovision Song Contest, but in case the artist is not available or refuses the offer, the organisers of the event reserve the right to choose another participant via their own criteria.

Among the competing artists were former Eurovision Song Contest entrants Francesca Michielin and Ermal Meta, who represented Italy in 2016 and 2018 respectively.

To conform with European Broadcasting Union (EBU) rules governing the use of explicit language, several changes were made to the lyrics of "Zitti e buoni" as performed by Måneskin at the Sanremo Music Festival earlier in the year.

[7] Jury members may only take part in panel once every three years, and are obliged to confirm that they are not connected to any of the participating acts in a way that would impact their ability to vote impartially.