The pressure fluctuations of high-speed centrifugal pumps are the hotspot in pump research. Pressure fluctuations is differ for different structural designs and flow structures. High-speed centrifugal pumps are usually designed to increase efficiency with an enlarged flow design at a low specific speed, which changes the structure of the pump. In order to analyze the pressure fluctuations of a high-speed centrifugal pump with an enlarged flow design, the pressure was measured, and the flow field of the pump was simulated with different flow rates. Through analysis, we found that pressure fluctuations varied periodically and was consistent with the blade frequency. The pressure fluctuations at the guide vane and the interference region were also closely related to the vortices at the impeller outlet, which changed differently at different flow rates. The results showed that the high-speed centrifugal pump with an enlarged design had better performance at a large flow rate. The results in this paper can provide reference for the design of a pump that should be designed with the enlarged flow method.