As one of hazardous wastes, the ever-increasing number of spent hydrodesulfurization (HDS) catalysts which consists of a considerable amount of heavy metals, such as vanadium (V), molybdenum (Mo) along with nickel (Ni) and other organic contaminant has presented a serious waste-management challenge. In this study, we propose the Fe₂O₃-assisted oxygen microbubble Fenton-like process for spent HDS catalysts recovery. The leaching efficiencies of vanadium, molybdenum, and nickel are close to 89%, 90%, and 97%, respectively, under the optimum operating conditions (Fe₂O₃/raw materials mass ratio 4%, pH 3.2, temperature 80 °C, liquid to solid mass ratio 15/1 and leaching time of 90 min). The advantages of this strategy are two fold: (i) using commercial oxygen and Fe₂O₃ as oxidants, avoid high costs and consumption of oxidants, (ii) oxygen microbubbles are introduced into the system and the free radicals (HO^•) generated by microbubbles collapsing during aeration enhance the mass transfer and oxidizing rates. However, the presence of strong reductive free radicals (H^•) makes microbubbles incompatible for use. Moreover, Fe₂O₃ is proven to promote the generation of HO^• from collapsing oxygen microbubbles under acidic conditions. These findings significantly increase the potential use of microbubble technique in resource recovery and provide fundamental information for peer researches to facilitate their future research on the development of more efficient and cleaner technologies.