Abstract: The machining surface quality will greatly affect the service life of parts. In this paper, the surface roughness of nickel-based superalloy GH4169 is reduced during the processing process and the milling parameters of the nickel-based superalloy GH4169 are optimized. Based on the response surface method, the influence law of milling parameters (speed, feed rate, cutting depth) on surface roughness is analyzed. The quadratic polynomial model between milling parameters and surface roughness is established and verified, and the optimal process parameter combination to reduce the surface roughness is determined. The results show that when A=928.34 r/min, B=243.35 mm/min and C=0.2 mm, the roughness can reach 0.143 μm. The processing experiments are conducted by using the optimal parameter combination, and then the surface roughness after milling is measured. The relative error between the measured roughness and the predicted roughness is 0.2%, which shows that the established model is accurate. The model can satisfy the surface quality characteristics of some high precision aerospace parts, so it has guiding significance for GH4169 milling.