Initially a member of Christian Democracy, the ruling party of post-war Italy, Schifani joined Berlusconi's Forza Italia in 1995.

On at least two occasions, he had been associated with people who were convicted of Mafia offences, though Schifani has never been directly investigated or indicted for any Mafia-related matters.

Filippo Mancuso, the former Italian Minister of Justice also born in Palermo, termed Schifani "the prince of debt collectors" (il principe del recupero crediti).

In 2002, Schifani was a protagonist in the attempt to secure the embedding of the provisional Article 41-bis prison regime,[1] which is used against people imprisoned for particular crimes such as Mafia involvement, as a definitive measure in Italian law.

On 19 March 2013, Schifano was appointed by acclamation as the group leader of Berlusconi's new party, The People of Freedom (PdL), in the Senate.

[1] On 4 August 2016, he joined the new Forza Italia, which had been established as the successor of the PdL in 2013, and thanked Berlusconi for welcoming him back.

[1] Schifani and Antonio Maccanico, senator of The Olive Tree, gave their name to a bill aimed at granting immunity to the top five representatives of the state, including the then Italian prime minister Silvio Berlusconi, who was the only one to not face trial.

The lodo Schifani decree was then approved in June 2003 by the Italian Parliament guaranteeing immunity to Silvio Berlusconi.

[10][nb 1] In the 2019, the Supreme Court of Cassation rejected Schifani's slander damages against Travaglio and Tabucchi, describing their criticism as within the right of critique.

[13] Enrico La Loggia (who would later become Minister for Regional Affairs),[14] Benny D'Agostino, Giuseppe Lombardo, and Antonino Mandalà were among its shareholders.

[18][19] Lombardo was chairman and member of the board of Satris, a credit recovery agency whose shareholders were Ignazio and Nino Salvo, well known businessmen and Mafiosi of the Salemi family who had been arrested by prosecutor Giovanni Falcone in 1984.

The master plan of the town of Villabate was designed under specific instruction of Mandalà and his son, who was responsible for the logistics to keep the fugitive Mafia boss Bernardo Provenzano at large.

[13] On 10 May 2008, the journalist Marco Travaglio interviewed on the RAI current affairs talk show television programme Che tempo che fa talked about the Italian media and mentioned past relationships between Schifani and men who have subsequently been condemned for Mafia association as an example of a relevant fact that in his view was ignored by almost all Italian newspapers that published a biography of Schifani as the new president of Senate.

[25] Schifani said that Travaglio's accusation was based on "inconsistent or manipulated facts, not even worthy of generating suspicions", adding that "someone wants to undermine the dialogue between the government and the opposition.

[30][31] As a tifoso and president of the Senate, he was present at Madrid when Inter Milan won the 2010 UEFA Champions League final.