Abstract: Since the response of storage tanks includes rigid body motion, impulse motion with middle and high natural frequency, convection motion with low natural frequency of storage liquid part, and structural motion of tower part, the storage tank system response is sensitive under the earthquake ground motion with broad frequency and high random parameters. In this paper, the seismic response of non-isolated model, story isolated model and base isolated model and its influential factors are studied by an optimal method. The governing motion equation of non-isolated model, story-isolated model and base-isolated model are built on Haroun-Housner theory. The optimal model, which is computed in MATLAB, is established using the mean and standard deviation of base shear as the objective function, and using the isolated period as the optimized parameter. Then the relationship between optimization model parameters and seismic response is illustrated. The influence rules are presented that the storage tank response is affected by the weight ratio of tank and tower, tower stiffness, tank aspect ratio and site classification. The research method and conclusion may be beneficial to isolated storage tank and improve the seismic performance of the tank.