Liquefied natural gas (LNG), stored by large-scale LNG storage tanks, could slosh and impact on the structure of storage tank, induced by earthquake and probably resulting in bulking failure and LNG leakage. However, the most existing researches on the isolation performance of LNG storage tanks fail to take fluid-structure interaction (FSI) into account seriously and it is not clear for the mechanism of FSI with the combination of isolation measures. Therefore, this study aims to investigate how FSI works in large-scale LNG storage tank respectively suffering from four kinds of seismic waves. A three-dimensional finite element model of a 200,000 m³ LNG storage tank was established in ANSYS, in which the LNG tank interaction and lead-rubber bearing (LRB) isolation system were considered. The results show that there are three main modes in LNG dynamic characteristics, namely the impulsive mode, the circumferential multi-wave mode and the convective mode. The specified lead-core rubber bearings (LRBs) could significantly alleviate the internal force of superstructure, especially more effective in cases of higher LNG liquid level. Nonetheless, LRB could be inevitably failure in the control of structural displacement and LNG slosh wave height and it’s suggested that other damping devices should be complementally utilized for preventing these risks.