Photodynamic therapy (PDT) holds promise in biochemical study and tumor treatment. A novel multifunctional nanosystem CaO2 /MnO2 @polydopamine (PDA)-methylene blue (MB) nanosheet (CMP-MB) was designed. CaO2 nanoparticles were encapsulated by MnO2 nanosheet, and then PDA was coated on the surface of CaO2 /MnO2 nanosheets, which could adsorb photosensitizer MB through hydrophobic interaction or π-π stacking. In this nanosystem, CaO2 /MnO2 had the ability of self-production of oxygen, which solved the problem of tumor hypoxia largely. Moreover, it is worth mentioning that the fluorescence of MB was suppressed by MnO2 , while its emission was triggered in the simulated tumor microenvironment. Therefore, CMP-MB nanosheet could be used to switch-control cell imaging potentially. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide testing and Live/Dead assay confirmed CMP-MB nanosheet had fewer side effects without illumination while it destroyed Hela cell with the illumination of light. Vitro cell experiment demonstrated CMP-MB nanosheet could achieve tumor microenvironment responsive imaging and inhibit tumor cell growth under illumination effectively. Therefore, the system has great potential for PDT application and switch-control tumor cell imaging. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.