Polypropylene and nylon 66 are used widely and have the connecting needs, but they can not be welded by laser transmission welding because of polar differences and poor compatibility. Given this situation, maleic anhydride is grafted to the side chains of polypropylene to improve the welding performance between polypropylene and nylon 66. The preparation formulation and process of the graft modified polypropylene are introduced, and the mechanical and thermal properties of the graft modified polypropylene are tested. The graft modified polypropylene and nylon 66 are welded by laser transmission welding, which shows that the graft modified polypropylene and nylon 66 have good welding performance. Based on central composite experimental design, through response surface methodology, the mathematical model between laser power, welding speed, fixture pressure and the joint strength are established. At the same time, the interactive influence of welding process is revealed and the optimal process parameters are obtained.