Isolation bearings are a seismic strengthening technique widely applied in building structures. However, sliding isolation bearings are seldom used for the seismic protection of artifacts housed in museums. The purpose of this study is to investigate the ability of the designed sliding isolation bearing to protect museum artifacts during earthquakes considering floor acceleration amplification. To better explore the effect of the magnification of the floor acceleration response on the seismic performance of the sliding isolation bearing, a three-story reinforced concrete frame structure was constructed, and a sliding isolation bearing-showcase-artifact system was placed on the floor of the structure. The seismic effectiveness of the proposed system was then evidenced by carrying out shaking table tests. It was observed from the tests that the sliding isolation bearing can effectively reduce the peak input acceleration, thus ensuring the safety of the artifact. Moreover, a seismic fragility analysis method is developed to evaluate the seismic performance of the sliding isolation bearing in the museum-showcase-artifact system subjected to unidirectional ground motions. Furthermore, the influences of the horizontal stiffness and the sliding displacement limitation of the bearing on the protective effect of artifacts are discussed based on the seismic performance assessment of the sliding isolation bearing.