A witness said pick-up trucks mounted with anti-aircraft guns surrounded the building and a gun battle ensued.
A government official later said the fighting had ceased.
The attackers are said to be former rebels who fought to topple Col Gaddafi last year, who are demanding pay-outs promised under a reward scheme.
Most people inside the building fled, including the finance minister and the deputy prime minister.
Ashur Shamis, a media adviser to Prime Minister Abdurrahim al-Keib, told the BBC that the prime minister and other officials were safe and that the fighting - which lasted several hours - had ended.
Witnesses said the attack was being carried out by militia from Yafran, a town populated by members of the Berber ethnic minority located about 100km (60 miles) south-west of Tripoli.
"Many men encircled the building and opened fire against it with weapons including anti-aircraft cannons," a government employee told AFP news agency.
"Some men entered the premises and fired from inside," he added.
An interior ministry official said at least two security guards had been killed, and others were injured, in the ensuing battle.
As well as the cash hand-outs, the rebels are demanding that those wounded in the uprising last year are given medical treatment abroad.
The reward scheme was suspended last month amid allegations of fraud.
The building is no stranger to attacks - it is the second of its kind in the last two months - but that the latest one seemed more forceful.
The Libyan government has been trying to encourage thousands of militia members who took up arms against Col Gaddafi to disarm, amid concerns about stability.
Source: BBC News
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