Abstract: GH4169 was widely used in the manufacturing of aerospace hot end components. In order to improve the fatigue life of GH4169 workpieces and improve machining efficiency, an orthogonal experiment was designed between milling parameters and residual stress on the surface of the workpiece. Based on experiments, an empirical formula was established between milling parameters and surface residual stress, and the influence of milling parameters on surface residual stress was analyzed. In addition, genetic algorithm was applied to optimize the milling parameters with the expected values of surface residual stress and material removal rate as the optimization objectives. And the optimization results were experimentally verified. The results indicated that the cutting speed had the greatest impact on the residual stress in the X and Y directions. The influence of feed rate per tooth on the residual stress in the X direction was second,and the influence on the residual stress in the Y direction was the smallest. The influence of cutting depth on the residual stress in the X direction was the smallest, and the influence on the residual stress in the Y direction was the second. A smaller cutting speed and a larger feed rate per tooth were beneficial for obtaining the desired surface residual stress, and changes in cutting depth have a little impact on residual stress.The optimized milling parameter combination was: v_c=26.64 m/min, a_p=0.45 mm, f_z=0.10 mm/z, a_e=0.25 mm, The optimized milling parameters can reduce the residualstress on the surface of GH4169 material and improve cutting efficiency. It can provide a basis for the selection of milling parameters for GH4169 parts.