Based on soil-structure interaction model, the seismic dynamic response of tunnel in karst areas were performed by using viscous-spring artificial boundary and time history analysis method. In combination with the Menglian tunnel engineering on the Bao-Teng Highway in Yunnan, in different sizes and sites karst caves conditions, the dynamic responses of displacement and internal force on control points of the tunnel structure were obtained. The results show that comparatively large interal forces, under the high-intensity earthquake conditions, will appear on the side wall of the tunnel which through karst areas, less ones on arch crown and inverted arch parts, and the differential displacements of arch crown reach to the maximum. When the karst caves are located in the side of the tunnel, it make the seismic dynamic response get more large, which make the surrounding rock must be strengthened treatment. The results provide useful reference for the aseismatic design of tunnel.