The longitudinal direction of shield tunnels is prone to seismic damage due to excessive deformation under seismic action, especially in nonuniform stratum. In this paper, the longitudinal dynamic response of the tunnel under different seismic effects is calculated based on the longitudinal equivalent stiffness model using the stratigraphic load model, and the seismic indexes such as longitudinal corner, tube sheet and joint bolt stresses are verified. The calculation results show that the longitudinal seismic weakness of the shield tunnel is in the interface between soft and hard strata and karst development. The longitudinal axial force of the structure is larger during the longitudinal excitation of seismic waves, and the maximum bending moment is mainly in the vertical plane, i.e., the vertical bending moment. The axial force of the tunnel is smaller during the transverse excitation of seismic waves. The maximum bending moment is mainly the bending moment in the horizontal plane, i.e., the transverse moment. The South Lake section of the Two Lakes Tunnel has good seismic performance in the event of a rare earthquake with a 50-year exceedance probability of 2%. The investigation can guide the seismic design of the South Lake section of the Two Lakes Tunnel.