The selection of suitable nanozymes with easy synthesis, tumor specificity,m ultifunction,a nd high therapeutics is meaningful for tumor therapy.H erein, af acile onestep assembly approach was employed to successfully prepare an ovel kind of naturalp olyphenol tannic acid (TA) hybrid with mixed valence vanadium oxide nanosheets (TA@VO x NSs). In this system, VO x is assembled with TA through metal-phenolic coordination interaction to both introduce superior peroxidase-like activity and high near infrared (NIR) absorption owing to partial reduction of vanadium from V 5 + to V 4 + .T he presence of mixed valencev anadium oxide in TA@VO x NSs is proved to be the key for the catalytic reaction of hydrogen peroxide (H 2 O 2)t oCOH, and the corre-spondingc atalytic mechanism of H 2 O 2 by TA@VO x NSsi s proposed. Benefitting from such peroxidase-like activity of TA@VO x NSs, the overproduced H 2 O 2 of the tumor microenvironmenta llows the realization of tumor-specific chemodynamic therapy (CDT). As av alid supplementt oC DT,t he NIR absorption enables TA@VO x NSs to have NIR light-mediated conversion ability for photothermal therapy(PTT) of cancers. Furthermore, in vitro and in vivo experimentsc onfirmed that TA@VO x NSs can effectively inhibit the growth of tumors by synergistic CDT/PTT.T hese resultso ffer ap romising way to develop novel vanadium oxide-based nanozymes for enhanced synergistic tumor-specific treatment.