Long-distance buried pipelines inescapably go through seismic fracture zones which makes the buried pipelines be easily influenced by the diastrophism. Most of the existing studies only focus on the two-phase contact between pipeline and soil, and the mechanical behavior of the cross-fault pipeline under transportation condition has not been studied. In this paper, ADINA finite element software was used to establish a pipe-soil-fluid three-phase coupling model based on fluid-structure interaction (FSI), and the effect factors of mechanical response of cross-fault buried gas pipeline were studied. Results indicate the following conclusions: (1) The model considering the effect of fluid-structure interaction can effectively simulate the mechanical response of pipelines in the actual working condition. (2) It is safer for the pipeline to pass through the strike-slip fault, and the most dangerous to pass through the reversed fault. (3) When the fault displacement is less than 1.3m, the optimal angle range to pass through the strike-slip fault is 30° to 60°, otherwise the optimal angle range is 30° to 45°; the optimal angle range to pass through the normal fault is 30° to 60°; the optimal angle to pass through the reversed fault is 90°. (4) When passing through the reversed fault, the optimal buried depth of pipeline is 1m-1.5m. (5) When the fault displacement is less than 1.3m, a certain delivery pressure (8MPa) can enhance the ability of pipeline to resist the strike-slip fault dislocation.