At least 30 regime loyalists and 20 IS jihadists were killed in the fighting, which continued into this morning, the Syrian Observatory for Human Rights said.
The Britain-based group said the IS attack began late on Wednesday, with the jihadist group using at least one suicide bomber against a militia checkpoint during its advance.
"Heavy fighting is continuing, with shelling by both sides," Observatory director Rami Abdel Rahman said.
He said IS had taken control of two southern districts of the city.
Control of Hasakeh, a provincial capital, is divided between Kurdish militia and government loyalists.
Kurdish forces are mostly present in the city's north and northwest.
IS has sought repeatedly to enter Hasakeh, including earlier this month when it advanced to the southern outskirts of the city before regime forces pushed it back in heavy fighting.
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