Abstract: A 5 kW CO₂ laser was used to prepare Ni45 cladding layers on the surface of 42 CrMoA steel, and the effects of different process parameters on the quality of Ni45 cladding layers were investigated. Orthogonal test methods were used to optimize the process parameters for single-pass laser cladding. The orthogonal test results show that the scanning speed and the powder feeding volume have the greatest influence on the dilution rate, while the scanning speed and the laser power have the greatest influence on the melting height and the melting width, respectively. The uncracked parameters of Ni45 cladding layer were obtained through the preliminary pre-test, namely, the maximum melting height is 1.6 mm and the maximum melting width is 5 mm. The optimal parameters were obtained by analysis of variance（ANOVA） method with response prediction, which are 2100 W laser power, 300 mm/min scanning speed, and 8.87 g/min powder delivery rate under the condition of 600 L/h of carrier gas flow. Using the above parameters to carry out single-pass optimization experiments, the prediction error of the cladding size response model is all within the range of ±5.1%. It can prove that the optimization of the parameters of laser power, scanning speed and powder feeding rate has a significant effect.