Covalent organic frameworks (COFs) are a class of crystalline porous polymer composed of organic units developed in recent years. Due to their good porosity, modularity, crystallinity and biocompatibility, they show a good application prospect in tumor therapy. The porous channels with adjustable pore sizes of COFs make them become an ideal drug delivery material. In addition, COFs can also be used in photothermal therapy and photodynamic therapy in combination with photothermal agents and photosensitizers. This review systematically introduces the synthesis methods of COFs, including solvothermal synthesis, mechanochemical synthesis, microwave synthesis, ionothermal synthesis, interfacial synthesis, room temperature synthesis and nanoscale synthesis. According to the differences in the mechanism of tumor therapy, the applications of COFs nanocarrier system for tumor therapy were reviewed, including chemotherapy, photothermal therapy, photodynamic therapy and combined therapy, proving that the promising drug carrier can effectively improve the therapeutic effect of nanocarriers on tumors. In addition, the main challenges and development trends of the COFs in the field of tumor therapy are discussed. This review could inspire research to design more effective COFs nano-drug delivery systems and promote the development of tumor therapy.