In a Francis turbine, the guide vanes are arranged in the direction of flow behind the stay vanes. And as it is generally believed that the outlet angle of water after it flows through the spiral case and stay vanes is fixed, the flow and flow circulation are altered by changing the opening of the guide vanes so as to change the output of the turbine. The rotor-stator interaction effect induced by the interaction between the guide vanes and the runner of the Francis turbine was one of the main causes of the pressure fluctuation. The effect of guide vanes placement on pressure fluctuation in vaneless zone of Francis turbine was studied. In this study, the commercial software ANSYS CFX16.0 was used for the three-dimensional numerical simulation of the whole flow passage of a Francis turbine model in a power station. The turbulence model used in the calculation was the shear stress transport (SST) model. The independence between the total number of computational meshes and the timestep was verified to ensure the reliability of the calculation results. Five schemes with different diameters of the guide vanes distribution circle were proposed including D0/D1 (guide vane pitch circle diameter /diameter of runner inlet) equaling to 1.119, 1.128, 1.138, 1.144, and 1.15. The steady calculation results showed that, when the turbine was operating under the design condition, D0/D1 increased from 1.119 to 1.15, and the turbine efficiency and output showed a monotonically increasing trend, with the efficiency increased by 0.17 percentage point and output increased by 3.91kw. Twenty monitoring points were set up in the vaneless zone between the guide vanes and the runner to collect pressure fluctuation signals in the vaneless zone. By analyzing the characteristics of unsteady pressure fluctuations in the vaneless zone under design conditions of the five schemes, the optimal position of the guide vanes was determined. The numerical results showed that the pressure fluctuation amplitude at monitoring points in the same axial direction increased gradually from the top cover to the bottom ring. When the unit operated under the design conditions, by increasing the guide vane pitch circle diameter, the rotor-stator interaction between the guide vanes and the runner domain was weakened, and the pressure fluctuation amplitude in the vaneless zone between the guide vanes and the runner was reduced, thereby the stability of unit operation was improved.