Nanozymes with intrinsic enzyme-like characteristics have attracted enormous research interest in biological application, due to their higher catalytic stability and activity than many natural enzymes. However, there is still a lack of facile approach for real-time evaluating the catalytic activity of nanozymes in living system, which limits their application in precise treatment of disease. Herein, we develop a novel manganese-semiconducting polymer-based nanozyme (MSPN) with oxidase-like activity for dynamically reporting the catalytic activity of itself in acid-induced cancer therapy via ratiometric near-infrared fluorescence (NIRF)-photoacoustic (PA) molecular imaging. Notably, MSPN possess oxidase-like activity in tumor microenvironment, owing to the mixed-valent MnOx nanoparticles ((Mn II ) 1 (Mn III ) 1.56 (Mn IV ) 1.4 O 6.14 ), which can effectively kill cancer cells. Because the semiconducting polymer (PFODBT) is conjugated with oxidase-responsive molecule (ORM) via amide bond, the catalyitic activity of nanozyme can be correlated with the ratiometric sginals of NIRF (FL 695 /FL 825 ) and PA (PA 680 /PA 780 ). Therefore, our integrated catalyitic and imaging platform represents an innovative strategy that can not only achieve effective catalyitic activity in vivo, but also be used to real-time monitor the nanozyme acitivity itself, which may provide new ideas for predicating anticancer effiecncy of nanozymes in biological condition.