Under strong earthquake, underground structures are vulnerable to severely damage due to liquefaction of saturated sand. In order to study the effect of grouting reinforcement on seismic response of the shield tunnel in liquefiable soil, the numerical models of grouting reinforcement and non-grouting reinforcement were established by using FLAC3D software respectively. The seismic responses characteristics of internal force and deformation of the tunnel structure and excess pore water pressure of sand under strong earthquake were studied, and the mechanism of grouting reinforcement weakening liquefaction of sand around the tunnel structure was revealed. Finally, the effect of grouting reinforcement on seismic performance of tunnel structures with different buried depths in liquefiable sand was systematically expounded. The results showed that: the excess pore water pressure in the sand around the shield tunnel could be reduced by grouting, resulting in liquefaction occurred only at the springing of the shield tunnel. After grouting, liquefaction is likely to occur in the middle of the two-lane tunnel, but the impact on the tunnel structure is small because the liquefaction area is small and does not spread. The maximum lateral convergence of the tunnel structure is reduced by 60%~80%, and the large deformation that occurs when the tunnel structure is extruded by the strata is effectively controlled; with the increase of buried depths, the liquefaction of the soil around the tunnel is reduced, and the uplift of the tunnel structure is reduced, and the lateral deformation and the internal force are increased. The research results can provide theoretical basis and scientific reference for the control of sand liquefaction under strong earthquake.