As a highly efficient and environmentally friendly gas fuel, hydrogen has emerged as one of the most promising sources of energy. However, the hydrogen explosion limit is low, the explosion risk is high, and the production, storage and transportation processes are prone to explode. Therefore, it is necessary to explore hydrogen explosion inhibitor to prevent and mitigation hydrogen explosions. In this study, the synergistic effect of the combination of inert gas and ultrafine water mist on the suppression of hydrogen explosion was studied by using a standard 20 L spherical explosive container bomb. The results of the study indicate that the combined use of inert gas and ultrafine water mist yields better suppression effects in terms of explosion pressure, flame propagation speed, and flame cellular structure formation, compared to the use of a single inert gas. Inert gas and ultrafine water mist have synergistic effects, but the synergistic effect of N2 was significantly stronger than that of CO2. Through chemical kinetic simulation, it was found that the formation rate of O, H, and OH, which were three active free radicals, decreased significantly compared with that of the single inhibition condition in the process of inhibiting the hydrogen explosion reaction by inert gas and ultrafine water mist. The pairing of nitrogen with ultrafine water mist demonstrates a superior collaborative effect in comparison to the combination of carbon dioxide and ultrafine water mist.