A 3D finite element model of the Huaiyin third pumping station of the Eastern Route of the South-to-North Water Transfer is described in this paper. Two methods were used in the calculation and vibration analysis of the pumping station in both the time domain and the frequency domain. The pressure pulsation field of the whole flow passage was structured on the basis of pressure pulsations recorded at some locations of the physical model test. Dynamic time-history analysis of the pump house under pressure pulsations was carried out. At the same time, according to spectrum characteristics of the pressure pulsations at measuring points and results of free vibration characteristics analysis of the pump house, the spectrum analysis method of random vibration was used to calculate dynamic responses of the pump house. Results from both methods are consistent, which indicates that they are both reasonable. The results can be used for reference in anti-vibration safety evaluation of the Huaiyin third pumping station.