The Syrian Observatory for Human Rights said a four-man ISIL unit killed Abu Mohammed al-Ansari, his wife, daughter, brother and niece in a house in Ras al-Hosn late on Tuesday.
Ansari headed the Al-Qaeda-affiliated Al-Nusra Front in Idlib province.
His killing was the latest since January in clashes between the two extremist groups as they strive for supremacy in areas of northern Syria under rebel control.
The Observatory said that after Tuesday's murders, Al-Nusra fighters killed one attacker and captured two more, while the fourth blew himself up.
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It added that in Deir Ezzor province in eastern Syria, ISIL managed to take a village as it tries to regain ground lost in February.
Both Al-Nusra Front and ISIL were offshoots initially of the Al-Qaeda branch in Iraq before deteriorating ties between them in Syria erupted into violence.
Al-Nusra and other opposition groups have been fighting against ISIL across rebel-held provinces since the beginning of the year, angered by their abuses of civilians and other rebels.
Also on Wednesday, the Observatory reported nine regime air raids on Mleiha in southern Damascus and three against rebel-held districts of the central city of Homs.