Cytokines play a crucial role in the cancer immune cycle by influencing tumor antigen expression, immune cell activation, and cancer cell killing in the tumor microenvironment (TME). They are considered potential anti-cancer immunotherapies, with ongoing clinical trials exploring their efficacy and safety. This review examines the current status of major cytokines, including IL-2, IL-15, IL-12, IL-21, interferons, TGF-beta, and GM-CSF, in cancer immunotherapy. The analysis highlights the trends in clinical trials, the development of cytokine-based therapies, and the challenges in their clinical application. IL-2 is the most studied cytokine for cancer immunotherapy, with a long history of use. It is primarily used in hematological cancers and solid tumors, and its development has shifted from natural forms to fusion proteins and immunocytokines. IL-12 and IL-15 are also being developed as anticancer agents, with IL-15 showing particular promise due to its role in enhancing NK cell activity. TGF-beta, which promotes cancer progression, is being developed as an antagonist to enhance immunotherapy. GM-CSF is used in hematological cancers and solid tumors, with a focus on cell gene therapy. Despite their potential, cytokine-based therapies face challenges such as systemic toxicity, complex immune responses, and short half-life. However, advancements in technology, including fusion proteins, pegylation, and cell gene therapy, are improving their efficacy and reducing side effects. These innovations are expected to enhance the clinical use of cytokines in cancer immunotherapy. The review emphasizes the importance of combining cytokine therapies with other treatments to maximize their effectiveness and address the challenges in clinical application.Cytokines play a crucial role in the cancer immune cycle by influencing tumor antigen expression, immune cell activation, and cancer cell killing in the tumor microenvironment (TME). They are considered potential anti-cancer immunotherapies, with ongoing clinical trials exploring their efficacy and safety. This review examines the current status of major cytokines, including IL-2, IL-15, IL-12, IL-21, interferons, TGF-beta, and GM-CSF, in cancer immunotherapy. The analysis highlights the trends in clinical trials, the development of cytokine-based therapies, and the challenges in their clinical application. IL-2 is the most studied cytokine for cancer immunotherapy, with a long history of use. It is primarily used in hematological cancers and solid tumors, and its development has shifted from natural forms to fusion proteins and immunocytokines. IL-12 and IL-15 are also being developed as anticancer agents, with IL-15 showing particular promise due to its role in enhancing NK cell activity. TGF-beta, which promotes cancer progression, is being developed as an antagonist to enhance immunotherapy. GM-CSF is used in hematological cancers and solid tumors, with a focus on cell gene therapy. Despite their potential, cytokine-based therapies face challenges such as systemic toxicity, complex immune responses, and short half-life. However, advancements in technology, including fusion proteins, pegylation, and cell gene therapy, are improving their efficacy and reducing side effects. These innovations are expected to enhance the clinical use of cytokines in cancer immunotherapy. The review emphasizes the importance of combining cytokine therapies with other treatments to maximize their effectiveness and address the challenges in clinical application.