In order to make a study on the work-hardening problem in the micro-milling machining GH4169, a three-dimensional (3D) micro-milling model is established based on ABAQUS software. The influence of the change in the feed per tooth and the spindle speed on the work hardening of the workpiece micro-groove along the reverse milling face was analyzed. The result of this research proves that within the range of experimental parameters, as the feed per tooth increases, the degree of hardening of the workpiece on the up-milling side and the down-milling side decreases. And when the spindle speed increase, the hardening degree on both sides of the tank shows a trend of decline as a whole. During the up-cut milling, the degree of hardening is slightly higher than that of crushing; On the other hand, the degree of hardening on both sides of the microgroove gradually decreases in the depth direction. The research results can provide reference for reasonable choice of GH4169 micro-milling processing parameters, and can also provide ideas for the study of material work hardening through finite element analysis(FEA).