We have developed a novel and facile approach of hydrothermal redox reaction to prepare cryptomelane-type octahedral molecular sieve (OMS-2) nanorods with tunable concentration of oxygen vacancy defects (OVDs). We demonstrate a giant OVD effect on the catalytic performance of OMS-2. Increasing the OVD concentration considerably enhances the lattice oxygen reactivity, thus tremendously promoting the catalytic activity for the oxidation of benzene.