Laser cladding process parameters are important to the quality of cladding layer, but the interaction between parameters is not clear. In this work, the effects of parameters, especially interaction, on laser cladding of Ti-B4C coating were studied by orthogonal experiments. And the optimal process parameters were obtained by GABP-NSGAII multi-objective optimization algorithm. The results show that the interaction (B4C content and laser power) had the greatest effect on the coating aspect ratio, cladding angle, and dilution rate. The microhardness of the coatings prepared with the optimum parameters of 15 wt%, 2200 W, and 800 mm/min is 434 HV0.5, which consists of columnar, dendritic, and equiaxial structures from the interface to the surface, respectively. The interaction affects the molten pool flow and the distribution of unfused B4C particles, and influences the concentration and distribution of reinforcing phases in the coating, as well as the heat input and phase transitions in the heat affected zone. This paper provides a reference for the preparation of high-performance and high-quality titanium matrix composite coatings by laser cladding.