Encapsulation of active biomolecules and/or nanoparticles in metal-organic frameworks (MOFs) remains a great challenge in biomedical applications. In this work, through a stepwise in situ growth method, a black phosphorus quantum dot (BQ) and catalase were precisely encapsulated into the inner and outer layers of MOFs, respectively. The integrated MOF system as a tandem catalyst could convert H2 O2 into O2 in MOF-stabilized catalase outer layer, and then O2 was directly injected into MOF-sensitized BQ inner, leading to high quantum yield of singlet oxygen. Upon internalization, the photodynamic therapy efficiency of the MOF system was 8.7-fold greater than that without catalase, showing an enhanced therapeutic effect against hypoxic tumor cells. Furthermore, by coupling with photothermal therapy of BQs, photodynamic-thermal synergistic therapy was realized both in vitro and in vivo.