In order to research the stability response mechanism of highway slope under the simultaneous action of rainfall and earthquake, the geotechnical simulation software GeoStudio is used to analyze the slope stability under the coupling of rainfall and earthquake with a high slope as the engineering background. The results show that: 1) When the rainfall intensity is 75 and 150 mm/d, the minimum average safety factor of the slope is 0.813 and 0.804, respectively; 2) When the seismic acceleration is 0.2 g and 0.4g, the minimum average safety factor of the slope is 0.786 and 0.804, respectively; 3) Under the action of earthquake, the slope undergoes three stages: elastic deformation, crack expansion and nonlinear deformation; 4) The main reasons for the reduction of slope stability is the reduction of the shear strength of the surface rock and soil caused by rainwater infiltration and the cracking of the rock and soil mass inside the slope caused by ground motion load. In the actual project, attention should be paid to the daily monitoring and protection of the slope. The results can provide some references for the daily disaster prevention and control of similar high highway slope projects.