In order to improve the safety of the hydrogenation station and provide a theoretical basis for the prevention and control of hydrogen leakage in the full-size hydrogenation station, taking a hydrogen refueling station in Shaanxi province as an example, the physical modeling was carried out by using ANSYS ICEM software, and the high-pressure hydrogen leakage process of hydrogenation station under the influence of different factors was simulated and analyzed in ANSYS FLUENT software. The results show that different leakage locations of different containers affect the flow of hydrogen gas cloud and the amount of hydrogen leakage. The leakage direction has obvious influence on the flow diffusion trend, which directly determines the flow direction of the hydrogen gas cloud. Take the high-pressure hydrogen storage tank as an example, when the leakage diameter increases from 10 mm to 20 mm, the leakage amount increases, the distribution range of hydrogen gas cloud expands, and the mass flow rate also increases. When the external wind speed is increased from 2 m/s to 10 m/s, the disappearance time of the hydrogen gas cloud increases first and then decreases. Barriers and walls can effectively limit the flow of hydrogen and prevent further expansion of accidents. But with the accumulation of hydrogen, the existence of barriers and walls will increase the risk of accidents. The research results provide countermeasures and suggestions for the hydrogen leakage accident in the hydrogenation station, and provide theoretical guidance for the operation and safety management of hydrogenation station.