Based on the design of the large-scale shaking table test of an underground pipeline under three dimension seismic excitation, the dynamic response of the soil-structure is analyzed by using ANSYS. In the numerical simulation, Drucker-Prager constitutive model is adopted to simulate the soil, the interface between soil and pipeline are simulated with zero thickness contact elements, size effects of test box are diminished by defining viscoelastic boundary around soil, the acceleration time history curve of the original earthquake wave is compressed and processed according to using the model scale similarity and energy duration which is presented by Trifunac-Brady [1] , and then the characteristic of seismic response of the pipeline can be found. The results show that the top of pipeline is the seismic response intense regional, deformation displacements of the central areas at the bottom and top of pipeline are always larger than others, the entrance and exit are the weak positions of anti-seismic structure; moreover, the dynamic response and interactions of soil-pipeline in the model experiment can be more accurately simulated by the methods presented in the paper. Thus, it can be served as reference for the design and construction of subsurface structures.