As a typical landform in loess regions, the loess hillock poses severe challenges to seismic hazard prediction and prevention because of its complex response mechanisms and potential failure modes under earthquake actions. By integrating relevant geological data from the Xi—Hai—Gu area (Ningxia, China), a generalized model of loess hillock slope was established. Using the ground motion from the Jishishan earthquake as dynamic input and a three-dimensional numerical simulation method, the three-dimensional seismic response and the patterns of instability and failure of the loess hillock slope were systematically analyzed. The results indicate that this slope exhibits a distinctive dynamic response pattern under seismic excitation. Compared with seismic intensity, the earthquake spectrum characteristics have a greater influence on the slope response. Under strong earthquakes, the slope initially experiences unilateral tensile cracking and sliding, which subsequently develops into an arc-shaped sliding surface throughout the slope. The findings of this study provide data support and theoretical guidance for seismic design in loess regions and contribute to the establishment of precise slope stability evaluation criteria and disaster prevention and control measures, thus helping mitigate the risk of earthquake-induced geological hazards.