Excessive production of intracellular reactive oxygen species (ROS) can induce apoptosis of cancer cells; however, it is often limited by severe triggering conditions and hypoxic microenvironments of solid tumors. To address these issues, herein, we have designed a MOF-coated upconversion nanoconstruct (UCTSCF, referring to UC@Ce6/TFS@mSiO2@MIL-100(Cu/Fe)) for synergetic photochemodynamic therapy (PCT)/oxygen-elevated photodynamic therapy (PDT). The MOF (MIL-100(Fe)) coating with Cu-doping was designed to catalyze H2O2 overexpression in cancer cells to generate the most cytotoxic ˙OH via chemodynamic therapy (CDT). It is noted that UC, representing 808 nm driven upconversion nanoparticles with high tissue penetration depth/low over-heating effects, was designed to provide intense blue light which can relieve the severe triggering conditions of CDT via PCT. Furthermore, the functional layer of the photosensitizer chlorin e6 (Ce6) and O2-carrying triethoxy(1H,1H,2H,2H-nonafluorohexyl)silane (TFS) co-doped mesoporous silicon (Ce6/TFS@mSiO2) can cause oxygen-elevated 1O2 production upon 671 nm light irradiation. In such a simple ROS generation nanoplatform, we heighten the antitumor effect via oxygen-elevated synergetic tumor PCT/PDT.