Applying base isolation technology to the design and construction of nuclear power plants can not only achieve standardized design of the upper structure, internal equipment and pipelines, shorten the design and construction time, and improve the economic efficiency of construction, but also increase the seismic margin of the structure, which is beneficial for the site selection and construction of nuclear power plants in high-intensity earthquake areas. This article takes the DA building of HPR 1000 as the engineering background, analyzes the mechanical performance of lead rubber bearings based on different restoring force models, and determines reasonable parameters of lead rubber bearings; Based on the layout characteristics of the DA building, analyzing and determining the optimal foundation isolation layout plan; Based on the optimal layout plan, considering the soil-structure interaction and conducting research on base isolation, analyzing the sensitivity of foundation parameters and isolation effect; Comparing the results of finite element simulation with the experimental data of the vibration table to verify the accuracy of the finite element simulation method. Through research, it has been found that the dynamic analysis of lead rubber based on the bilinear restoring force model is more in line with the actual mechanical performance of the bearings; The use of base isolation technology can effectively reduce the horizontal seismic response of the structure and its ancillary equipment, and the isolation effect is obvious; By comparing and analyzing the finite element simulation results with the vibration table test results, the overall results match well. As the first domestic application of base isolation technology in the HPR 1000, this study provides good engineering reference and beneficial design experience for the seismic isolation design and research of subsequent nuclear power plants.