Masked gunmen opened fire on two relatives sitting in a vehicle in the Arab village of Jaljulia on Monday morning, killing one man and seriously wounding the second.
A large number of bullets were fired at the vehicle during the attack, police said.
The victims, aged 25 and 30, are known to police due to alleged criminal activity.
Local residents rushed the casualties to Petah Tikva's Beilinson Hospital.
Police have launched a manhunt for the attackers.