The laser welding test with Sn powder addition was carried out on DC56D+ZF galvanized steel with thickness 1.4 mm and 6016 aluminum alloy with thickness 1.2 mm. By using optical microscopy, scanning electron microscopy, X-ray diffraction and tensile test, the microstructure, fracture morphology, interface element distribution, main phase and mechanical properties of joints were studied. Elastic moduli and thermodynamic properties were calculated by using first-principles method based on density functional theory for FeAl and FeSn compounds. The results indicate that the morphology of welding surface can be improved and grain size is fine when the welding power is 2000 W, welding speed is 45 mm/s, the defocus distance is +2.0 mm, and Ar gas acts as the protection gas with flow rate 15 L/min. The average shear strength of the welding sample with Sn powder reaches 62.17 MPa. Compared to that without Sn powder addition, the average shear strength of weld joint increases by 1.46 times. Because of fine-grain strengthening and the improvement of the fluidity of the molten pool metal with Sn addition, it promotes the combination of the steel and aluminum interface and decreases the thickness of the intermetallic layer. FeSn intermetallic compounds has better ductility and is more stable than that of FeAl at high temperature that retard and reduce the generation of Fe-Al intermetallic compound, which can improve the mechanical properties of weld joint with Sn addition.