Hassan Nasrallah said Saudi Arabia had declared war on Lebanon, and was holding Mr Hariri against his will.
He also accused the Saudis of inciting Israel against Lebanon.
The powerful Hezbollah Shia movement is an ally of Iran, which has been trading accusations with the Saudis of fuelling tension in Lebanon and the region.
Mr Hariri said in a TV broadcast from Riyadh on Saturday he was stepping down because of an unspecified threat to his life. He also attacked Hezbollah and Iran.
However, Lebanese President Michel Aoun and other senior politicians have demanded his return, amid suspicions that he is being held by the Saudis under house arrest and forced to do their bidding.
Mr Aoun has not accepted Mr Hariri's resignation.
Mr Hariri has still not spoken publicly since his announcement.
Mr Nasrallah said at the weekend that Mr Hariri had been forced to resign by the Saudis, but he repeated the allegations on Friday, saying that this was now "beyond any doubt".
Saudi Arabia was attempting to remove Mr Hariri as prime minister and impose a new leadership on his political movement, he said.
"We condemn the blunt, bare-faced Saudi intervention in our domestic affairs," Mr Nasrallah said.
"Any offence to the Lebanese prime minister is an offence to all Lebanese, even when he is our adversary."
Mr Hariri's Future Movement is seen as opposed to Hezbollah politically, even though they both sit in government.
Mr Nasrallah also accused Saudi Arabia of being prepared to pay "billions" to Israel for a military strike against Lebanon, describing this as the "most dangerous thing".
Mr Hariri (R) was seen meeting the Saudi king on Monday
On Thursday, French President Emmanuel Macron paid an unscheduled visit to Saudi Arabia.
France has historical ties with Lebanon, as its former colonial power before it gained independence during World War Two.
There are fears Lebanon could become embroiled in a wider regional confrontation between Saudi Arabia and Iran.
Tensions between the three countries have soared since Mr Hariri announced his resignation.
On Thursday, Saudi Arabia and its Gulf allies told their citizens in Lebanon to leave the country immediately.
The move came after Riyadh accused Iran of "direct military aggression", saying it supplied a missile which it says was fired by Hezbollah at Riyadh from Yemen on Saturday.
Iran has dismissed the Saudi allegations as "false and dangerous".