It is urgent to exploit multifunctional materials and combined approaches for efficient antitumor effects. Copper-based metal-organic frameworks (Cu-MOFs) have excellent performances in catalysis, biocompatibility, photothermal conversion, and regulate metabolism, which make them attract more and more attention in antitumor application. Therefore, in this review, representative ligands, synthetic methods, antitumor mechanism, and antitumor applications of Cu-MOFs were provided. Special emphasis is placed on the recent antitumor applications of Cu-MOFs in drug carriers, antitumor therapy, tumor imaging, and theranostic, which are summarized with examples. Finally, we presented the dilemma faced by Cu-MOFs and offered a new perspective for future antitumor application. Hopefully, this review may serve as a reference for further development and application of Cu-MOFs.