The hotel in the center of Qamishli has functioned as a municipality building, according to a Kurdish official in the town, Joan Mohammed.
The area has been the scene of heavy battles recently between Kurdish gunmen and members of the al-Qaida breakaway group, the Islamic State of Iraq and the Levant.
Syria's state-run SANA news agency said three people died in the attack on the Hadaya Hotel. It didn't provide further details.
Mohammed, the Kurdish official, said there were multiple casualties in the attack but that he didn't have exact figures.
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"The building is in the center of the town and is usually very crowded," said Mohammad, adding that Kurdish fighters in the area were "on high alert" following the attack. He spoke to The Associated Press by phone from Qamishli.
There was no immediate claim of responsibility, but suspicion immediately fell on the Islamic State of Iraq and the Levant. Militants from the group have been fighting Kurdish gunmen for months in northern Syria in battles that left hundreds of people dead.
Also today, the Syrian government acknowledged it had freed women prisoners in exchange for 13 Greek Orthodox nuns who had been held by al-Qaida-linked rebels. But Information Minister Omran al-Zoubi said the government freed only 25 prisoners and not the 150 reported by foreign mediators.
"The real number of those who were freed in exchange for the release of the nuns, who were kidnapped by armed terrorist gangs, is 25 persons," he told Syrian state TV.
Qatari and Lebanese officials, who were mediating between Damascus and the rebels holding the nuns, said previously that 150 women prisoners were released yesterday.