"I announce my resignation from the post of prime minister," he said in a speech broadcast from Saudi Arabia by the Al-Arabiya news network.
"I felt what was being covertly plotted to target my life," Hariri said.
Saad Hariri named Lebanon's new prime minister
The two-time prime minister, whose father Rafik was assassinated when he held the same position in 2005, accused Iran and its powerful Lebanese ally Hezbollah of seeking hegemony in the region.
The 47-year-old politician's resignation comes less than a year after his government, to which Hezbollah's political wing belongs, was formed.
"Iran has a grip on the fate of the region's countries... Hezbollah is Iran's arm not just in Lebanon but in other Arab countries too," he said.
Lebanese army: no coordination with Hezbollah, Syria in IS attack
"In recent years, Hezbollah has used the power of its weapons to impose a fait accompli," he said, reading a speech from behind a desk.
Hezbollah is a vital ally of Syrian President Bashar al-Assad in the war the Syrian regime is waging against the Islamic State group and armed opposition movements.
It enjoys broad support from Iran and is the only Lebanese party to have kept its weapons after the 1975-1990 civil war.
Its arsenal has since grown exponentially and now outstrips that of the nation's own armed forces.
Iran building weapon factories in Syria and Lebanon, claims Israel
It claims it is the only credible rampart against neighbouring Israel and its refusal to disarm is the main political crux in Lebanon.
Hezbollah members have been accused over the 2005 assassination in a massive car bomb blast of Rafik Hariri, the dominant figure of Lebanon's post-war political landscape.
He made his fortune in Saudi Arabia, where his son Saad was born. Riyadh is Iran's main regional rival and the two powers' tussle for influence has played out in ongoing conflicts in Iraq, Syria and Yemen.
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