Large Liquefied Natural Gas (LNG) tanks are prone to damage during strong earthquakes, and accurate seismic analysis must be performed during the design phase to prevent secondary disasters. However, the seismic analysis of large LNG tanks is associated with high computational requirements, which cannot be satisfied by the calculation efficiency of traditional analytical techniques such as the Coupled Eulerian–Lagrangian (CEL) method. Thus, this paper aims to employ a less computationally demanding algorithm, the Smoothed Particle Hydrodynamics-Finite Element Method (SPH-FEM) algorithm, to simulate large LNG tanks. The seismic response of a 160,000 m3 LNG prestressed storage tank is evaluated with different liquid depths using the SPH-FEM algorithm, and simulation results are obtained with excellent efficiency and accuracy. In addition, large von Mises stress at the base of the tank indicates that strong earthquakes can severely jeopardize the structural integrity of large LNG tanks. Therefore, the SPH-FEM algorithm provides a feasible approach for the analysis of large liquid tanks in seismic engineering applications.