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The high-speed railway has become an important passenger transport mode. Relying on the abundant passenger transport experience and expansive railway network, the high-speed freight train (HSFT) is feasible to be developed and has great application potential. As a critical component of HSFT, the cargo plays an important role in the overturning safety of HSFT under strong wind conditions. Previous studies about the aerodynamic performance of the high-speed train usually regarded the loaded carbody as an individual rigid body. Limited attention was paid to the variability inside the vehicle. In order to improve the running safety of HSFT under strong wind conditions, the multibody dynamics simulation is adopted to demonstrate the effect of cargo property on the overturning risk of HSFT under the aerodynamic loads obtained through the computational fluid dynamics (CFD) simulations. It is demonstrated that the inner side crosswind is more dangerous than the outer side crosswind. The speed of HSFT should be limited according to the cargo quantity, and the maximum speed for a fully loaded HSFT can be 305 km/h when the crosswind velocity is 20 m/s. The larger cargo density should be encouraged because it is good for train overturning safety in severe working conditions.