Renzi, 39, who presents himself as an outsider to Italy's largely discredited political class, said conservative forces would not halt his plans to reform the public administration and change labour rules.
"It's clear that a large part of the ruling class is against us," the leader of the centre-left Democratic Party (PD), told the Corriere della Sera daily.
As campaigning heats up ahead of the European elections this month, Renzi's PD is competing with the overtly anti-establishment 5-Star Movement, which is the second-largest party behind the PD and is gaining ground in opinion polls.
Renzi took aim at trade unions protesting against his proposals for changes to labour rules, and political critics who say his planned cuts in income tax are not properly funded and will put public finances at risk.
His broad left-right coalition agreed last week to make it easier for firms to keep temporary workers and apprentices on their books for extended periods without offering them permanent contracts.
The proposals are still before parliament, but critics in Renzi's PD and among the trade unions are already up in arms.
They say the plans go in the opposite direction of reforms by former Prime Minister Mario Monti who tried to discourage firms from using temporary contracts which offer workers low pay and few rights.
Renzi dismissed the unions' protests as an unacceptable defence of the status quo.