Cave excavation in the pumped storage power plant building is usually carried out by the technique of drilling and blasting. In this study, a part of the pumped storage power plant building was analyzed by the blasting simulation with the Ls-Dyna. Three different explosive arrangements were considered, and comparative analyses of the damage and cumulative effects on the surrounding rock were carried out, including blasting effects, damage analysis, and stress response. The results show that the blasting effects of three arrangements are basically similar and meet the requirements of excavation blasting for the project. However, compared with Cases 1 and 3, the damage level of Case 2 (cruciform arrangement) on the perimeter rock was reduced by 22.3 and 29.5%, respectively. The pressure waves generated by the blast were less superimposed and caused less damage to the upstream and downstream protective layers. Therefore, Case 2 represents the best explosive arrangement for blasting machinery room, which can minimize damage and ensure safety and stability during excavation and blasting.