Reactive oxygen species (ROS) can kill cancer cells in tumor therapy. However, the anticancer efficacy of ROS is generally suppressed by the reductive press in tumor microenvironment (TME). Herein, lysozyme (LZM) modified black phosphorous (BP) /manganese dioxide nanosheets (LZM@BP/MnO 2 NSs, LBM) as an effective and biocompatible nanodrug platform for synergistic photodynamic-/radio-therapy are prepared. The controllable preparation of negatively charged MnO 2 NSs is achieved through biomimetic mineralization strategy using bovine serum albumin (BSA) as a template. To facilitate the loading of BP on MnO 2 , lysozyme is used to modify BP to obtain positively charged BP NSs. The as-obtained LBM possess higher biostability and exhibit superior ROS generation efficiency to BP, owing to the alleviation of reductive species (i.e., GSH) in TME by the oxidation of MnO 2 . Moreover, LBM can be easily decomposed in the tumor sites, leading to the good biocompatibility both in vitro and in vivo. The amplified intracellular ROS generation properties of LBM assisted combination of photodynamic therapy and radiotherapy ultimately boost the synergistic therapeutic efficacy against cancer.