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In order to analyze the influence of the stiffness change of the long-span track bridge on running safety of the train, a bridge and train analysis model, based on Chongqing Egongyan track bridge, is established to simulate and evaluate the spatial coupling dynamic response of the wind–train–bridge system through stiffness change and to propose the reasonable stiffness limit range of the long-span track suspension bridge. The results show that the dynamic characteristics of the bridge are good, and the safety of train operation and ride comfort meet the requirements when the vertical stiffness is 1/300–1/500 and the lateral stiffness is 1/600–1/1200; the dynamic response of the bridge and the running safety of the train are significantly sensitive to the stiffness change of the bridge, especially when the wind speed is 25 m/s and the vertical stiffness is 1/300, at this time, the derailment coefficient and the wheel load reduction rate reach 0.72 and 0.54, respectively, which are close to the limit standard, indicating that there are some potential safety hazards in train operation. [ABSTRACT FROM AUTHOR]