To investigate the pressure pulsation characteristics of self-priming pumps under different flow conditions, Fluent 19.2 software was used to numerically calculate the internal flow inside a self-priming pump by means of the RNG k-ε model. The pressure pulsation characteristics, as well as the standard deviation in the volute and impeller domains, were analyzed under different flow conditions. As a result, under rated- and high-flow conditions, the monitoring points in the volute channel have obvious periodic patterns, and the peak pressure pulsations all occur in the octave band of the blade frequency. The pressure pulsation amplitude is larger under the high-flow condition than in the other two conditions. The monitoring points L1 and L5 on the impeller channel centerline are located near the impeller’s inlet and outlet, respectively, so the pressure pulsations are larger than other monitoring points.