In order to adapt to the new needs of China’s energy structure adjustment and batch construction of nuclear power, the number of nuclear-related engineering projects has increased significantly in recent years. In the actual project, there are some nuclear-grade plant super-heavy large equipment due to the differences in body size, height and centre of gravity, the distribution of the centre of mass is not regular, and there are fewer studies on the calculation method of the impact of the equipment sub-structure and plant coupling and decoupling on the structural stress under the seismic effect. Based on ANSYS finite element analysis software, this paper establishes coupling and decoupling two kinds of equipment substructure analysis models, calculates and analyses the typical components of “HPR1000” NX nuclear auxiliary plant, and researches the influence of different calculation methods on the internal force and reinforcement of plant components under the same seismic action, and completes the differential analysis of the coupling and decoupling of equipment substructures of plant components. The results show that the main direction bending moment of the coupled model is larger than that of the decoupled model, while the main direction membrane force and overall reinforcement ratio are lower than that of the decoupled model. For the nuclear plant with heavy equipment, it is more appropriate to use the coupled model for the overall seismic calculation and local stress analysis.