During the flood season, Francis turbines often operate under low-head and full-load conditions, frequently experiencing significant pressure pulsations, posing potential threats to the safe and stable operation of the units. However, the factors contributing to substantial pressure pulsations in Francis turbines are multifaceted. This paper focuses on a mixed-flow hydroelectric generating unit at a specific hydropower station. Field tests were conducted to investigate abnormal vibrations and hydraulic pressure pulsations under low-head and full-load conditions. Utilizing the Navier–Stokes equations and the RNG k-ε turbulence model, the unsteady flow field within the turbine under these conditions was calculated. The results indicate that the abnormal pressure pulsations detected in the bladeless zone between the wicket gates and the turbine inlet are due to operational points deviating from the normal operating range of the turbine. When water flows at a large inflow angle, striking the turbine blade heads, it leads to significant flow separation and vortex formation at the back of the blade inlet edges, causing severe vibrations in the hydroelectric generating unit. These findings provide a basis and assurance for the safe and stable operation of the power station.