By leveraging the ability of Shewanella oneidensis MR-1 (S. oneidensis MR-1) to anaerobically catabolize lactate through the transfer of electrons to metal minerals for respiration, a lactate-fueled biohybrid (Bac@MnO ) was constructed by modifying manganese dioxide (MnO ) nanoflowers on the S. oneidensis MR-1 surface. The biohybrid Bac@MnO uses decorated MnO nanoflowers as electron receptor and the tumor metabolite lactate as electron donor to make a complete bacterial respiration pathway at the tumor sites, which results in the continuous catabolism of intercellular lactate. Additionally, decorated MnO nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H O ) into generate oxygen (O ), which could prevent lactate production by downregulating hypoxia-inducible factor-1α (HIF-1α) expression. As lactate plays a critical role in tumor development, the biohybrid Bac@MnO could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.