Cancer is a serious threat to human health and life safety. The number of cancer patients has been increasing worldwide. Therefore, it is of great significance to develop efficient cancer treatment methods. Currently, the main clinical methods for cancer therapy include surgery, radiotherapy, chemotherapy, immunotherapy, and so on. In recent decades, nanomaterials-based cancer treatment methods have shown great potential and value in radiotherapy, chemotherapy and immunotherapy. Metal-organic framework (MOFs) is a kind of material composed of metal nodes and organic ligands. The metal-organic frameworks have many advantages, such as large porosity, adjustable aperture and size, good biocompatibility, adjustable composition and surface modification, which make it promising in the field of cancer therapy. In this review, the methods for constructing MOFs-based drug delivery system (DDS) were firstly introduced. In particular, small molecule drugs can be efficiently loaded into metal-organic frameworks using non-covalent penetration, covalent cross-linking, and so on. At the same time, biomacromolecules-MOF system could be constructed based on the methods such as pore-penetrating and de novo approach. MOF-enzyme complex is more resistant to hush circumstances or protein inactivating agents than naked enzyme. Moreover, the metal-organic framework itself can be designed to be highly efficient nano-drug by using pharmaceutically active organic molecules or metal ions as ligands or metal ions. General surface modification methods were also reviewed due to their important roles for improving the solubility and stability of MOF-based DDS. In this review, recent numerous researches on the cancer therapy of MOF-based DDS have been summarized. According to the type of treatment methods, the applications of MOF-based DDS in chemotherapy, photodynamic therapy, biomacromolecules-MOF based therapy, and other combined therapies (such as radiotherapy, and immunotherapy) for cancer were introduced, respectively. Finally, we summarized the advantages and challenges of MOFs in cancer therapy, and prospected the opportunities and development of this research field.