Hydraulic vibrations in Francis turbines caused by cavitation profoundly impact the overall hydraulic performance and operational stability. Therefore, to investigate the influence of cavitation phenomena under high-load conditions, a three-dimensional unsteady numerical simulation is carried out for a Francis turbine with different head operating conditions, which is combined with the SST k-w turbulence model and two-phase flow cavitation model to capture the evolution of cavitation under high-load conditions. Additionally, utilizing entropy production theory, the hydraulic losses of the Francis turbine during cavitation development are assessed. Contrary to the pressure-drop method, the entropy production theory can quantitatively reflect the characteristics of the local hydraulic loss distribution, with a calculated error coefficient τ not exceeding 2%. The specific findings include: the primary sources of energy loss inside the turbine are the airfoil cavitation and cavitation vortex rope, constituting 26% and 71% of the total hydraulic losses, respectively. According to the comparison with model tests, the vapor volume fraction (VVF) inside the draft tube fluctuates periodically under high-load conditions, causing low-frequency pressure pulsation in the turbine’s power, flow rate, and other external characteristic parameters at 0.37 Hz, and the runner radial force fluctuates at a frequency of 1.85 Hz.