Earthquake excitation is a kind of complicated multi- dimensional motion, so it is not safe and accurate enough to only consider horizontal earthquake excitation. Unlike ordinary ground motions, far- field long- period ground motions have characteristics such as long period, long duration, and rich low- frequency components. They will have adverse effects on structures with large isolation periods. The soil- structure interaction (SSI) is particularly complicated and needs further discussion. Therefore, a large chassis inter- story isolation structure was established in this paper. Under the excitation of three- dimensional ground motion, the different effects of ordinary earthquakes and far- field long- period earthquakes on the inter- story isolation structure were discussed, and the different effects of SSI on the structure were analyzed. The results show that the seismic response of three- dimensional long- period far- field ground motion on the inter- story isolated structure is far greater than that of ordinary ground motion. When the SSI effect is considered, the structural response increases with increasing soil softness. Three- dimensional isolation bearings were set to solve the problems of traditional horizontal isolation bearing under three- dimensional far- field long- period ground motion, i.e., story drift ratio and bearing displacement beyond limits. The analysis results show that the isolation effect of three- dimensional isolation bearings is better than that of traditional horizontal isolation bearings.