The rare flare-up in the Kurdish-majority city near the Turkish border saw 11 regime fighters and seven Kurds killed, the Kurdish security forces known as Asayesh said in a statement.
The Syrian Observatory for Human Rights, a Britain-based war monitor, reported the same death toll for the fighting near a Kurdish checkpoint in the city.
The Asayesh said a regime "patrol opened fire on our forces with light and medium weapons, causing our forces to respond to this violation, which killed 11 regime fighters... and seven of our comrades".
The Observatory said the shootout started when Asayesh members at the checkpoint asked regime fighters aboard a patrol vehicle to step out but they refused.
"When they did not comply, the shooting started on the car," Observatory chief Rami Abdelrahman said, and the clashes escalated after both sides called in reinforcements.
An AFP correspondent at the scene saw empty camouflaged pick-up trucks in the street.
Some bore bullet holes, while traces of blood were visible on the tarmac, he said.
Kurdish forces control most of Qamishli, but regime forces and allied militiamen hold part of the city and its airport.
Deadly clashes last broke out between Kurdish forces and pro-regime fighters in Qamishli in April 2016, but ended days later with a truce.
That fighting began with a scuffle at a checkpoint and, according to Kurdish security forces, killed 17 civilians, 10 Kurdish fighters and 31 regime troops and militia.
With US-led support, Syria's Kurds played a prominent role in the war against the Islamic State group during which they seized large swathes of northern and northeastern Syria where they have set up automous institutions.
The Damascus regime has vowed to reintegrate the Kurdish-held areas, by force if necessary.
In late July, it opened talks with the Kurdish-led Syrian Democratic Forces on a negotiated settlement.
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