Rehman Malik said the government was seeking Musharraf's arrest because he allegedly failed to provide adequate security for Bhutto, who was killed in a gun and suicide bomb attack in 2007.
Musharraf, a one-time U.S. ally, went into self-exile in Britain in 2008 after being forced out of the presidency he secured in a 1999 military coup. The current government is being run by Musharraf's political rivals, and the president is Bhutto's widower.
Musharraf, who wants to return to Pakistan to contest elections likely this year, told a local television channel that the government was playing politics over the case. Musharraf has repeatedly denied any legal responsibilty for the killing.
A Pakistani court issued an arrest warrant for Musharraf last year over the allegations.
Legal expert Hashmat Habib said Interpol has the right to detain Musharraf and hand him over to Pakistan if it chooses to issue a warrant. But it is unclear how the international police organization will respond, or indeed whether Malik will go ahead with his threat.
The former prime minister was killed on Dec. 27, 2007, shortly after returning to Pakistan to campaign in elections Musharraf agreed to allow after months of domestic and international pressure.
A U.N. investigation into the assassination said Musharraf's government didn't do enough to ensure Bhutto's security. It criticized steps taken by investigators after her death, including hosing down the crime scene and failing to perform an autopsy.
The U.N. officials were not tasked with finding out who the exact culprits behind the killing were. But they identified two main threats facing Bhutto -- Islamist extremists like al-Qaida and the Taliban who opposed her links to the West and secular outlook, and members of the "Pakistani Establishment," the term used locally to refer to a powerful and shady network of military, intelligence, political and business leaders said to actually control the country.
After her death, Bhutto's Pakistan People's Party rode a wave of public sympathy to garner the most seats in the February 2008 elections. Months later, the party forced Musharraf to step down as president by threatening impeachment, and the presidency was eventually won by Bhutto's widower Asif Ali Zardari.
Musharraf later left for London, and has since spent a good deal of time on the lecture circuit, including in the United States.