The pressure pulsation due to rotor-stator interaction (RSI) is unavoidable for high-speed centrifugal pump when operating under different conditions. The frequency components of pressure pulsation in the vaneless region are the most complex, and the pressure pulsation characteristic plays an important role in pump structural stress analysis. A numerical simulation method is used to obtain the hydraulic performances of a high-speed centrifugal pump with 9857 r/min at the range of flow rates between 48.1 to 155.0 m3/h. The head and efficiency under different operating conditions have good agreement with experimental results, with maximum deviations in 3.82% and 5.37%, respectively. The results show that the level of the pressure pulsation from the inlet to the outlet of the impeller increased gradually, and the pressure pulsations between the short blades are greater than that between the long and short blades. In the diffuser, the pressure pulsation is the highest near the tongue, whereas it is lower in the region between the two tongues, and this region is defined as the vaneless region. The pressure contours in the vaneless region almost have no change, while they near the tongue are densely distributed, revealing the mechanism of uneven pressure pulsation distribution. Moreover, there is a high radial velocity distribution near the tongue in the vaneless region, indicating that there may be a jet-wake pattern occured in this region.