Francesco Pannofino was born in Pieve di Teco, in Liguria. As a teenager, he discovered his comedic talent and began to perform in theatres with small companies. At just 14 years old, he moved to Rome and got his start in radio and dubbing. He continued to pursue acting and joined Antonella Steni's company, after a stint at the Teatro Stabile in Trieste. In the 1980s he found success alongside Gigi Angelillo and Ludovica Modugno, with whom he formed a comedy trio. In the 1990s, he lent his voice to Tom Hanks in Forrest Gump and Denzel Washington in Philadelphia; these two films propelled him to voice actor stardom and he became the voice of George Clooney and Antonio Banderas, among others. On Italian TV, he appears in some of the most popular series, such as Carabinieri and La Squadra. In the 2000s, he played in Cristina Comencini's Liberate i pesci!, Davide Marengo's Notturno Bus, Genovese and Miniero's Questa notte è ancora nostra, Claudio Cupellini's Lezioni di Cioccolato, Fausto Brizzi's Maschi contro femmine, and Ogni maledetto Natale by Giacomo Ciarrapico, Mattia Torre and Luca Vendruscolo. He took part in the production of Sky's cult series Boris, which also made it to the cinema. He played in Cesaroni and Un medico in famiglia and plays the main character in the series Nero Wolfe. In 2013 he was in Adriano Olivetti: La forza di un sogno by Michele Soavi. On TV, he hosted the 2012 Concerto del Primo Maggio. He was also in Emigratis, Miss Italia: Gli esami and narrated for the ratings record-breaking programme Meraviglie: La penisola dei tesori. On the twentieth anniversary of the Harry Potter saga, he lent his voice to the audio book of the complete series by J. K. Rowling. In summer 2018, he performed in the Aristophanes comedy The Knights on stage at the Greek Theatre in Syracuse and toured with G. Clementi's play Bukurosh, mio nipote. He was in the cast of the films Il caso Pantani and Nati due volte. He was the voice of Animali fantastici: Dove trovarli on Audible. He graced the stage of Teatro Piccolo Eliseo with Io vendo le emozioni. He also performed in Si muore solo da vivi, on TV in Tale e Quale Show and in Fox's Romolo + Giuly: La guerra mondiale italiana. He voices Klaus in the Netflix animated film of the same name. He was the narrator for Sky Arte's project Io, Leonardo. Since 2020 he has been on tour with Mine Vaganti and participates in the programmes Moviemagic and E poi c'è Cattelan. He was in Il tempio della velocità directed by T. Cenname, as well as Quelle brave ragazze. He returned to his iconic role in Boris 4. In 2021 he performed in the following films: E. Ivone's Ostaggi, A. Ferrari's The Christmas Show, F. Albanese's Uomini da marciapiede, G. Amato's Lo sposo indeciso che non poteva (o forse non voleva) uscire dal bagno, L. Gualano's La guerra del Tiburtino III.