Abstract: Large centrifugal pumps are characterized by high design flow rates and high heads, and significant pressure pulsations are generated inside the unit during start-up and shut-down processes. Since the discharge chamber, suction chamber, and stay ring are directly embedded in concrete, these pressure pulsations have a significant impact on the powerhouse structure. To investigate the vibration response characteristics of the powerhouse and pump unit during start-up and shut-down, this study employs the SST k-ω turbulence model to numerically simulate the transient flow field during pump start-up and shut-down. The transient pressure on the surfaces of the discharge chamber, suction chamber, and stay ring under start-up and shut-down conditions is used as the load, and a time-history analysis method is applied to conduct coupled vibration analysis of the pump and the overall powerhouse structure. The results show that the deformation of the discharge chamber and the powerhouse follows a consistent trend with the internal pressure changes in the discharge chamber. The maximum deformation of the discharge chamber occurs at the outlet, while the maximum deformation of the powerhouse occurs in the concrete surrounding the discharge chamber, both of which occur when the guide vane opening is small. The vibration is most significant at the pump floor closest to the unit, and it gradually decreases from the pump floor to the cable gallery as the distance from the discharge chamber increases. However, above the cable gallery, due to the whipping effect of the powerhouse's own structure, the vibration increases with increasing distance from the unit. The findings of this study provide an important theoretical basis for the safety evaluation and design optimization of powerhouse structures.