Seismic uplift of a high-speed rail (HSR) cable-stayed bridge’s bearing affects train safety. Existing technique lacks improved seismic isolation in the vertical direction due to the bearing’s vertical stiffness. Based on the on-site dynamic test and train derailment table experiments and different software, the train running safety of the semi-floating system of the cable-stayed bridge-rail-train system was analyzed using different damping and isolation control strategies. The larger vertical seismic component increases the danger of flange climb derailment when subjected to near-fault earthquakes. After installing lateral/or viscous fluid dampers (VFDs) and magnetorheological (MR) bearing (A = 3.0), the bridge has an obvious bearing uplift response. Still, it is not enough to threaten the structure, and the seismic damping capacity of the bridge structure is improved, making the train ride safe. This research presents discoveries on the impact of bearing uplift on train operational safety. Specifically, it reveals that the lifting of the end bearings on both sides of the main girder is not synchronized. This investigation presents a technical reference for comparable initiatives.