The vertical volute centrifugal pump is widely used in the long-distance water division project. Flow separation and vortex phenomenon can be observed in the vertical volute centrifugal pump at stall operating conditions. This kind of unsteady flow structures would result in the instability of the pump unit which affects the safety and reliability of the unit operation. In order to obtain the relationship between the stall characteristics of the pump and the different guide vane openings, a comparative study of the guide vane openings and the stall phenomenon of the vertical volute centrifugal pump was carried out. Based on the SST-SAS turbulence model with refined mesh, the unsteady flow patterns and induced pressure fluctuation in the pump were simulated under the conditions of small opening, optimal opening and large opening of the guide vane, and the influence of the guide vane opening on the stall characteristics of the vertical volute centrifugal pump was analyzed. The research results showed that the SST turbulence model combined with the selected grid can be validated in the experimental verification during the steady calculation. The performance results predicted by the SST-SAS turbulence model showed quite good agreement with the experimental data, and the prediction errors were less than 5%. The stall characteristic operating points were the same at different guide vane openings. The flow-head curve showed a typical hump area, but the positive slope corresponding to the flow-head curve was the largest when the guide vane opening was small, and the smallest when the guide vane opening was large. Under the three kinds of guide vane openings, the vortex in the vaneless area between the guide and stay vanes was serious, and the flow separation on the working surface of the stay vane continued to spread to the back of the adjacent stay vane. At the same time, the distribution law of fluid entropy production rate in the impeller was significantly different at different openings under the deep stall condition. As the opening of the guide vane increased, the flow separation area in the impeller blade near the shroud was enlarged. And under the conditions of the optimal opening and large opening, a large velocity gradient appeared in the middle section of the impeller blade near the impeller flow channel exit, the characteristics of high local entropy production rate were caused. The main frequency of the pressure fluctuation under the deep stall condition at small opening was the blade passing frequency 7fn, while the main frequency at the optimal opening was 0.9fn, and the corresponding amplitude of the frequency was large in the range of 0.7fn~1.2fn at the large opening. The pressure fluctuation at the large opening showed broadband characteristics. Through the unsteady numerical simulation results, it was found that the appearance of low-frequency pressure fluctuation was closely related to the periodic large-scale vortices in the vane diffuser.