The operating state of a pump-turbine unit under no-load conditions is directly related to its safe and stable operation. In order to probe into the influence of hydraulic characteristics on structural performance, a pump-turbine assembled in China is selected for research by using CFD (computational fluid dynamics) and unidirectional FSI (fluid–structure interaction) methods. The vortex distribution and the law of pressure pulsation propagation are analyzed to capture the peculiar flow phenomena. The results show that the vortex distribution in the runner channel appears initially at the suction side of the blades but then propagates toward the pressure side with GVO. This produces rotating stall frequencies (0.7fn) and a combination of the RSI, asymmetry of the water ring in vaneless space, and high-amplitude pressure pulsations in the downstream channel close to the runner inlet and elbow section of the draft tube. This, in turn, is associated with the structural stress of the runner and guide vane. The stress level of the guide vane becomes alleviated under no-load conditions with large GVO, but the stress distribution of the runner is no longer symmetrical, which aligns with the vortex evolution in the runner passage. The stress concentration that develops further along the blade root increases the structural failure, which is also captured and verified as a crack in the prototype runner. The phenomena suggest that the RPT should avoid operating under no-load conditions with large GVO as far as possible. Therefore, in the design or optimization of the pump-turbine unit, the structures of the guide vanes and runner could be treated as a whole to investigate the resulting internal flow and structure characteristics.