In this work, the interfacial microstructure and fatigue properties of friction stir lap welding (FSLW) joint of 6061 aluminum (Al) alloy and QP1180 steel with a Ni interlayer were characterized, and the effects of Ni on the intermetallic compounds (IMCs) evolution and fatigue behavior were revealed. The results show that an Al-Ni transition layer with a thickness of ∼ 200 nm appears at the interface of Al-Ni-Fe joint. No Al-Fe IMC is formed in the joint, because the Ni interlayer effectively blocks the reaction between Al alloy and steel. The fatigue strength of Al-Ni-Fe joint is 50 % higher than that of Al-Fe joint. The failure modes of Al-Fe joints are affected by the load levels. The joint breaks at the interface at high load levels, while the joint tends to break along the thickness direction of Al plate at low load levels. After adding Ni interlayer, the joint breaks along the thickness direction of Al plate at both high and low load levels. Based on the theoretical calculation, all Al-Fe IMCs exhibit brittleness, and most of Al-Ni IMCs exhibit toughness. Hence, Al-Ni phases effectively prevent crack propagation by enhancing the interface bonding strength of Al alloy and steel, and improve the fatigue strength of joint.