Mr Nica was fired over comments about next month's presidential election
Romania's coalition government has collapsed after the Social Democrat Party (PSD) resigned, officials say.
The leftist coalition partner said it had pulled out in protest against the sacking of the interior minister.
The PSD's Dan Nica was this week fired by centrist PM Emil Boc after he made comments about the potential for fraud in presidential elections next month.
Party leader Mircea Geoana said all PSD ministers in government were resigning to protest against his dismissal.
Although Mr Boc's Liberal Democrats (PD-L) can rule as a minority government for a few weeks, they will have to seek parliament's approval for the appointment of new ministers.
The crisis has raised the prospect of the country failing to meet conditions set by the International Monetary Fund for emergency aid worth 20bn euros (£18.4bn; $27bn).
Romania, which has been hard-hit by the global economic recession, is dependant on an IMF loan to pay state-sector salaries, and has seen recent protests by railway workers and magistrates.
Mr Geoana announced the mass resignation by PSD ministers after an emergency party meeting on Thursday.
"The president succeeded in triggering a political crisis," he said.
President Traian Basescu had attempted to mediate between the two parties by suggesting a neutral figure replace Mr Nica at the traditionally PSD-run interior ministry.
But Mr Boc instead replaced Mr Nica with his own party's Vasile Blaga, who is close to the president.
The comments that led to Mr Nica's dismissal were seen as a suggestion that Mr Boc's party might try to cheat to get the president, who has links with the PD-L, re-elected.
The two parties had ruled in coalition since elections last December.