The National News Agency said Mohammed Chatah and his driver were both killed in the explosion, which wounded more than 70 others.
Lebanon has seen a wave of bombings over the past months as tensions rise over Syria's civil war. Hariri heads the main, Western-backed coalition in Lebanon which is engaged in bitter feuding with the militant Hezbollah group, which is allied to Syrian President Bashar Assad.
The blast was heard across the city and sent thick black smoke billowing in the downtown posh commercial district behind the government house and above the seafront of the Lebanese capital. The army cordoned off the area to prevent people from getting close to the scene, where the twisted wreckage of several cars was still smoldering. The explosion appeared to be the result of the car bomb, but security officials said they had no immediate confirmation.
Footage broadcast on Lebanese TV showed medical workers rushing the wounded to ambulances. At least two bodies could be seen lying on the pavement.
The conflict next door has raised tensions in Lebanon's Sunni and Shiite communities as each side lines up in support of their brethren in the conflict next door.
That has fueled predictions that Lebanon, still recovering from its 15-year civil war that ended in 1990, is on the brink of descending into full-blown sectarian violence.
Chatah, a prominent economist and former ambassador to the U.S., was one of the closest aides to former Prime Minister Rafik Hariri, who was killed in a truck bombing in Beirut in 2005, not far from Friday's explosion.
He later became finance minister when Hariri's son, Saad, took over the premiership, and stayed on as his senior adviser after he lost the post in early 2011.
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