Monoclonal antibodies contain an antigen-binding fragment (Fab) and a crystallizable fragment (Fc). Currently, many studies have modified monoclonal antibodies to regulate the interaction between antibodies and the immune system and further improve the therapeutic effect of the tumor. Compared with traditional chemotherapy drugs, therapeutic monoclonal antibodies have the characteristics of high targeting and low toxicity side effects and are an essential auxiliary means of tumor therapy. Among the modification methods, modification of the Fc part of monoclonal antibodies is an important one. The Fc part can recognize and bind to immune cells expressing Fc receptors and bind to the complement components in blood. Compared with traditional monoclonal antibodies, Fc-modified monoclonal antibodies can enhance or weaken the affinity to the receptor and affect the half-life of antibodies and the biological activity of antibodies through antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytotoxicity (ADCP), complement-dependent cytotoxicity (CDC) and other mechanisms. Among the Fc-modified monoclonal antibodies for cancer treatment in clinical practice, most of them exhibit better anti-tumor potential by affecting the affinity of monoclonal antibodies to their binding Fcγ receptor (FcγR), thereby affecting the function of Fc segment and enhancing or weakening the ADCC effect. In most cases, a monoclonal antibody can kill tumor cells mediated by the ADCC effect, so enhancing the ADCC effect can improve the efficacy of monoclonal antibodies in tumor treatment. However, in monoclonal antibodies that target to block cell surface receptors or cytokines, such as immune checkpoint inhibitor antibodies, the immune response mediated by FcγR and complement may affect the efficacy, and some attenuation of the ADCC effect is required. Currently, the widely used engineering modification methods of the Fc segment include the following directions: the modification of antibody protein sequence, such as protein engineering technology based on amino acid substitution; the modification targeting the post-translational modification of antibody protein, which mainly uses glycosylation modification technology; in addition, the modification of the structural framework of IgG subclasses selecting the framework of new IgG subclass (such as IgG4) to replace the traditional one of IgG1 also exerts function by affecting the affinity of the Fc segment to their FcγR. Many studies have demonstrated that compared with traditional monoclonal antibodies, Fc modified monoclonal antibodies have certain advantages in the clinical and fundamental data of tumor therapy, showing good antitumor activity in breast cancer, hematologic tumors, lung cancer and other tumors. Here, the authors systematically demonstrate the classical structures of monoclonal antibodies, the mechanisms of action as well as the main strategies for Fc part modification of the monoclonal antibody drugs, the clinical application and development prospects.