Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@CoO-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified CoO nanoparticles decorated metal-organic framework PCN-224. CoO can catalyze the decomposition of highly expressed HO in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@CoO-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@CoO-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@CoO-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.