Pumped-storage power technology is currently the only available energy storage technology in the grid net, and its reliability is receiving attention increasingly. However, when a pump-turbine unit undergoes runaway transitions, hydraulic fluctuations intensively affect the reliable operation of a pumped-storage power station. To reduce hydraulic fluctuations, this study investigated the formation mechanism of hydraulic fluctuations and explored its influence factors. In this study, a developed one-dimensional and three-dimensional (1 D-3D) coupling simulation method was adopted. Transient runaway transitions of a pump-turbine with three different inertias (0.5 J, 1 J, and 2.0 J) at three different guide vane openings (21°, 15°, and 12°, respectively) were simulated and compared. The results suggest that, at smaller guide vane openings (15° and 12°), water hammer owing to the increase in rotational speed is the primary unstable issue compared to the pulsation of radial hydraulic exciting forces on the runner. However, at a larger guide vane opening (21°), the latter owing to the back-flow near the runner inlet is the primary unstable issue. Moreover, it is found that a sufficiently large inertia improves the hydraulic fluctuations of the pump-storage power station, particularly in reducing the pulsation of radial hydraulic exciting loads on the runner. The findings of this study provide a valuable reference for determining suitable rotor inertia.