The anticancer effect of photodynamic therapy (PDT) in tumors is affected by intratumoral hypoxia and acidic microenvironment. Manganese dioxide (MnO2) has excellent oxidation-reduction (REDOX) and catalytic capacities, which can response to tumor microenvironment to release oxygen and improve the therapeutic effect of PDT. In this study, nanocomposites MnO2-Ce6@TPP-LND (MCTL) were obtained by using MnO2 nanosheets as the framework material and loading with photosensitizer Ce6 and lonidamine (LND) modified by triphenylphosphine (TPP). The synthesized MCTL showed relatively uniform sizes as well as good H2O2 and pH response characteristics. Compared with Ce6 alone, MCTL exhibited higher enrichment in tumor cells. After combining with PDT, the production of reactive oxygen species by MCTL enhanced and the damage of tumor cells aggravated, ultimately leading to the significant decrease of tumor cell survival rate. These results provide experimental basis for the clinical application of MCTL in photodynamic therapy against tumor.