Abstract: The deep penetration lap welding of 304 stainless steel/5052 aluminum alloy was carried out with laser-MIG hybrid welding. The effects of nickel interlayer with different penetration on cross section morphology, microstructure and mechanical properties of interface layer were studied. Experimental results showed that the addition of nickel interlayer would worsen the 304/5052 joint under the condition of low penetration. Under the condition of medium penetration and high penetration, the addition of nickel interlayer could effectively inhibit the formation of Fe-Al intermetallic compounds（IMCs） and reduce the thickness of IMCs in the interface layer. Nickel atom could replace some iron atoms to form Al₃Ni, which could reduce the brittleness and hardness of IMCs. After adding nickel interlayer, the tensile strength of the joints with low penetration became lower, the tensile strength of the joints with medium penetration increased but the increase range was not obvious,and the tensile strength of the joints with high penetration increased obviously.