The FeO nanozyme, the first reported nanozyme with intrinsic peroxidase-like activity, has been successfully employed for various diagnostic applications. However, only a few studies have been reported on the therapeutic applications of the FeO nanozyme partly due to its low affinity to the substrate HO. Herein, we report a new strategy for improving the peroxidase-like activity and affinity of the FeO nanozyme to HO to generate reactive oxygen species (ROS) for kidney tumor catalytic therapy. We showed that cobalt-doped FeO (Co@FeO) nanozymes possessed stronger peroxidase activity and a 100-fold higher affinity to HO than the FeO nanozymes. The lysosome localization properties of Co@FeO enable Co@FeO to catalyze the decomposition of HO at ultralow doses for the generation of ROS bursts to effectively kill human renal tumor cells both and . Moreover, our study provides the first evidence that the Co@FeO nanozyme is a powerful nanozyme for the generation of ROS bursts upon the addition of HO at ultralow doses, presenting a potential novel avenue for tumor nanozyme catalytic therapy.