A series of nano-ZnO desulfurizers were prepared by the homogeneous precipitation-gradient calcination method. The synergistic optimization of particle size (10–50 nm) and oxygen vacancy concentration was achieved by regulating the calcination temperature. The material structure was systematically characterized by XRD, TEM, XPS, MS-H₂S-TPSR and other techniques, and its desulfurization performance for H₂S at room temperature was investigated. The results showed that the nano-ZnO prepared by calcination at 350℃ (particle size 22 nm) had the highest oxygen vacancy density, with a room-temperature sulfur capacity of 18.5%, which was about 4 times higher than that of traditional micro-ZnO. Mechanism studies indicated that oxygen vacancies could adsorb and activate O₂, oxidizing H₂S into polysulfide intermediates (ZnSₓ), which were ultimately converted into easily regenerable elemental sulfur instead of directly forming ZnS. After 5 cycles of use, the sulfur capacity of the desulfurizer remained 15.2%, showing good stability and regeneration performance, which provided new materials and a theoretical basis for low-temperature efficient desulfurization.