"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.
The two-time prime minister, whose father Rafik held the same position for years and was assassinated in 2005, accused Iran and its powerful Lebanese Shiite ally Hezbollah of seeking hegemony in the region.
The 47-year-old Sunni 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.
"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.
Hariri accused Tehran of "sowing discord among the children of the same nation and creating a state within the state... to the extent that it gets the final say on how Lebanon's affairs are run."
Hezbollah is a vital ally of Syrian President Bashar al-Assad in the war the Syrian regime is waging against ISIS 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.