For the problem that 50Cr5NiMoV alloy steel was prone to damage defects such as cracks and holes during forging process, its hot deformation behavior and critical damage characteristics were systematically investigated. Then, the high-temperature tensile tests were conducted by thermal simulator Gleeble-3800 to obtain the true stress-true strain curves under the deformation temperature of 900-1200 ℃ and the strain rate of 0.001-1 s-1, and the Arrhenius constitutive equation was established by linear fitting. Furthermore, based on the Normalized Cockcroft-Latham damage model and combined with Zener-Hollomon parameter, the critical damage values under different deformation conditions were determined, and the hot deformation fracture criterion of 50Cr5NiMoV alloy steel was constructed. The modified stress-strain curves and critical damage values were implemented in finite element software to simulate and analyze the upsetting process under different process parameters, and the actual processing process on site was compared. The research results demonstrate that the critical damage value increases with the increasing of strain rate, increases first and then decreases with the increasing of temperature, and reaches the maximum value at 1000-1100 ℃. During the upsetting process, the damage value increases with the increasing of deformation amount, and cracks appear at the riser end of ingot when it exceeds the critical value, which is consistent with the actual processing results. Thus, the research results provide a theoretical basis for the optimization of forging process and crack prediction of 50Cr5NiMoV alloy steel.