As one of the typical forms of loess landforms, the complex response mechanism and potential failure mode of loess mound under the action of earthquakes have brought severe challenges to the prediction and prevention of earthquake disasters. Based on the relevant geological data of Xihaigu area, the generalized model of Huangtumao slope is established, and the ground motion of Jishishan is selected as the dynamic input. The three-dimensional seismic response and instability failure law of Huangtumao slope are systematically analyzed by using three-dimensional numerical simulation technology. The results show that the loess hill slope shows a unique dynamic response mode under the action of earthquake. Compared with the seismic intensity, the seismic spectrum has a greater impact on the slope response ; under the strong earthquake, the slope first appeared unilateral tensile sliding, and then developed into an arc sliding surface of the whole slope. The results provide data support and theoretical guidance for the seismic design of loess areas, which is helpful to formulate accurate slope stability evaluation standards and disaster prevention