A pump is one of the most important machines in the processes and flow systems. The operation of multistage centrifugal pumps could generate pressure fluctuations and instabilities that may be detrimental to the performance and integrity of the pump. In this paper, a numerical study of the influence of pressure fluctuations and unsteady flow patterns was undertaken in the pump flow channel of three configurations with different diffuser vane numbers. It was found that the amplitude of pressure fluctuation in the diffuser was increased gradually with the increase in number of diffuser vanes. The lower number of diffuser vanes was beneficial to obtain a weaker pressure fluctuation intensity. With the static pressure gradually increasing, the effects of impeller blade passing frequency attenuated gradually, and the effect of diffuser vanes was increased gradually.