Seismic resilience of critical infrastructure, such as liquefied natural gas (LNG) storage tanks, is essential to the safety and economic well-being of the general public. This paper studies the effect of different ground motions on large LNG storage tanks under four different site conditions. Key parameters of structural design and dynamic analysis, including von Mises stress of outer and inner tanks, tip displacement, and base shear, are analyzed to directly evaluate the safety performance of the large LNG tanks. Because the size of an LNG tank is too large to perform any experiments on a physical prototype, Smoothed Particle Hydrodynamics-Finite Element Method (SPH-FEM) simulation is used as a feasible and efficient method to predict its seismic response. First, the accuracy of the SPH-FEM method is verified by comparing sloshing frequencies obtained from theoretical formulation to experimental results and SPH-FEM models. Then, the seismic response of a real-life 160,000 m3 LNG prestressed storage tank is evaluated with different liquid depths under four site classes. Simulation results show that the tip displacements of the LNG tank at liquid levels of 25% and 50% under site class IV are nearly identical to that of 75% and 100% under site class II. In addition, the maximum von Mises stress of the inner tanks exceeds 500 MPa in all four site classes and jeopardizes the structural integrity of large LNG tanks. As a result, optimization of structural design and the establishment of an early warning system are imperative to the safety of LNG tanks at high liquid levels.