Carbon Fiber Reinforced 1Plastic (CFRTS) and TC4 titanium alloy have excellent properties such as high stiffness, fatigue resistance and corrosion resistance, which are widely used in aerospace and new energy vehicle manufacturing. Due to the great differences in physical and chemical properties between CFRTS and TC4 titanium alloy, the traditional bonding and riveting methods have the problems of aging and stress concentration. This study introduces the interface composite control process of “picosecond laser cleaning and plastic-covered”. Firstly, CFRTS was subjected to laser cleaning pretreatment to remove the surface epoxy resin. Secondly, laser was used to pretreat the surface microstructure of TC4 titanium alloy. A layer of 0.02 mm PA powder was spread on the surface of the microstructure and melted by laser to form a plastic-covered layer. Finally, the treated CFRTS and TC4 titanium alloys were welded by laser-assisted joining. Compared with the traditional cleaning technology, it was found that the carbon fiber was exposed obviously and the structure was complete on the CFRTS surface after picosecond laser cleaning, and the epoxy resin was removed completely. The porosity of the joint interface is reduced, and the weld morphology is better. The shear strength of CFRTS-TC4 titanium alloy joint is significantly enhanced, and the maximum shear strength is 6333 N.