China is one of the countries with the most intense neotectonic movements in the world, with a wide distribution of active fault zones. Seismic damage data show that tunnels crossing fault fracture zones suffer particularly severe seismic damage. In this study, a tunnel crossing a fault fracture zone is taken as the engineering background. Based on the orthogonal experimental approach, numerical tests were conducted to investigate the variation of tunnel structural stress and displacement under different combinations of three factors: grouting reinforcement thickness of the surrounding rock, seismic joint width, and asphalt-cement damping layer thickness. Range analysis was used to compare the reduction in the maximum and minimum principal stresses and peak displacements of the lining under different combinations. Sensitivity analysis was also performed to determine the optimal seismic design combination. The results show that the dynamic response of a tunnel at a stratigraphic interface is more intense than that of a tunnel in a fault fracture zone. The three measures-grouting reinforcement of the surrounding rock, installation of a damping layer, and seismic joints-are all effective in reducing seismic vibrations. The importance ranking of the three factors is as follows: seismic joint width > damping layer thickness > grouting reinforcement of the surrounding rock thickness. For the background engineering of this study, the optimal seismic design combination for the tunnel crossing the fault fracture zone is a surrounding rock reinforcement range of 6 m, an asphalt-cement damping layer thickness of 0.2 m, and a seismic joint width of 0.2 m.