GH4169 is a high temperature resistant nickel based alloy with excellent properties, which is widely used in the manufacture of hot components of aircraft and spacecraft. Therefore, it shall be provided with high anti-fatigue properties. The residual stress in machining has great influence on the fatigue strength of the parts. The work aims to improve the selection of cutting parameters and further improve the fatigue life of these parts by studying the effects of cutting parameters on the residual stress during GH4169 high speed milling. A single-factor experiment was designed between GH4169 high-speed milling parameters and machining-induced residual stress. The varying pattern among residual stress on the workpiece surface, residual stress in direction of cutting depth and cutting parameters was obtained by adjusting one cutting parameter only with others unchanged. The surface residual stress in feed direction of milling (x-direction) and the vertical feed direction (y-direction) was mainly present as tensile stress, which increased as milling depth and feed per tooth increased, and decreased as the milling speed increased. Along the direction of cutting depth, the residual stress in two directions of the plane in which different cutting depth values were present was mainly compressive stress, which firstly increased and then decreased with the increase of cutting depth. Peak value of the residual stress increased with the increase of milling depth and feed per tooth, decreased with the increase of milling speed, the maximum depth of residual stress was less than 80 μm. To obtain less surface residual tensile stress during GH4169 high-speed miling, less milling depth, feed per tooth and larger milling speed shall be selected. In addition, in order to obtain a large residual compressive stress in the direction of cutting depth, larger milling depth, feed per tooth and smaller milling speed shall be selected and vice vers.