"The mafia is a pathological phenomenon that we want to defeat once and for all by the end of this term in office," Mr Berlusconi told Italy's national radio.
"No government in the history of the republic has acted with as much determination and efficiency in the fight against criminal organisations".
Italian police have arrested hundreds of people in recent anti-mafia raids.
Those being held are accused of extortion, arms dealing and drugs trafficking.
Earlier this month, mafia informant Gaspare Spatuzza made an allegation that a Sicilian Mafia boss convicted of 1990s bombings had boasted of ties to Mr Berlusconi.
Gaspare Spatuzza said the Mafia boss claimed to have Mr Berlusconi's support.
A spokesman for Mr Berlusconi, who denies the allegations, suggested the Mafia was trying to discredit the prime minister.