Accurate estimation of structural responses is important to mitigate loss of life and property. Earthquake ground motions are known to vary spatially and temporally, thereby affecting structural responses. Therefore, we conducted a numerical analysis based on a fault-structure system to account for such variations. We developed a full threedimensional model that includes a fault, irregular crust structure, soft soil basins near the ground surface, and structures at the surface. However, huge computational cost is required to solve these components simultaneously. Ichimura and Hori (2009a) presented a macro-micro analysis method based on singular perturbation expansion to reduce computational cost, but to date, no large-scale application examples have been conducted. We implemented a highly tuned finite-element method code for macro-micro analysis systems to handle large-scale wave propagation in a complicated crust structure as well as the seismic response of a structure at the surface. After verifying the accuracy by comparing the results with analytical Green's function solutions, we demonstrate a seismic response using a simple model of a nuclear power plant structure with actual settings. Our methodology can enable detailed prediction of the seismic response of a nuclear facility, permitting the generation of more reliable estimates of the seismic safety of new or existing nuclear power plant facilities.KEYWORDS: seismic analysis of nuclear power plant structure, fault-structure system, macro-micro analysis, hybrid grid finite element method