At least 45 people were killed and around 400 were wounded in street gun battles between Libyan militiamen and residents in the capital Tripoli on Friday, Alarabiya reported.
A peaceful demonstration demanding the militia to abandon a place it has occupied since Muammar Qaddafi's ouster in 2011 turned violent when the militia opened fire and killed two protesters.
A Reuters reporter saw an anti-aircraft cannon firing from the "Gharghur brigades'" gated compound into the crowd as protesters chanted: "We don't want armed militias!"
Demonstrators fled but then returned, heavily armed, to attack the compound, where the militiamen remained holed up past nightfall as fighting continued.
They entered the district of Gharghour where the headquarters is located "and set fire to all the villas (the militia) occupied so that they would not return," said one witness, who identified himself only as Ibrahim.
"Most of the members of the militia barricaded themselves inside one single villa, but the noose is tightening around them," he added.
The Health Ministry then reported that 13 people were killed and 285 were wounded.
Dozens of soldiers in trucks tried to separate the sides, and sealed off roads to stop more people joining the clashes.
Heavy smoke could be seen rising from the scene in the Gharghur district, where many of Qaddafi's closest collaborators used to live before the uprising, according to Reuters.
Prime Minister Ali Zeidan denounced the killing of protesters. "The demonstration was peaceful and had been permitted by the Interior Ministry, and then the protesters were fired on when they entered the Gharghur district," he said.
"Armed groups must leave"
"The exit of armed groups from Tripoli is not something up for debate but necessary and urgently needed," Zeidan told Reuters TV and the Libya Ahrar channel in an interview. He did not elaborate.
Libya's turmoil and the weakness of its border controls are worrying its North African neighbors. France this week said it was considering offering more counter-terrorism training and aid to help Libya prevent militancy spilling over its frontiers.
The French intervention in neighboring Mali this year drove some Islamist militants with links to al Qaeda across the border into Libya's lawless southern deserts, where the central government has little or no say.
So far, the capital has been spared the almost daily bombings and killings that plague Libya's second city, Benghazi, in the east. But when clashes between rival militias do break out, the nascent armed forces are no match for them.
The Misrata gunmen had fought twice last week with a rival group that had detained one of their members for driving a car without number plates.
On Friday, air force planes circled overhead during the clashes. "We want to make sure the militia doesn't bring in any reinforcements," said army spokesman Ali al-Sheikhi.
Strikes and armed protests around the country by militia and tribal gunmen demanding payments or more autonomy rights have also shut much of the OPEC member's oil output, depriving the government of its main source of income.
The authorities have tried to defuse the threat of the militias by placing them on the government payroll and assigning them to provide security.
But the gunmen often remain loyal mostly to their own commanders and fight for control of local areas, especially their weapons or drug smuggling rackets, or to settle personal feuds.
Zeidan was himself briefly abducted in October by a militia group on the government payroll.