Abstract: Tumor immunotherapy has brought about revolutionary changes in recent years, with immune checkpoint blocking and adoptive cell therapy gradually becoming the standard strategies for cancer treatment. Most cancer immunotherapies rely on cytotoxic CD8⁺ T cells for their anti-tumor activity, yet recent studies have found that the role of CD4⁺ T cells can,t be ignored. CD4⁺ T cells can assist CD8⁺ T cells to better exert their cytotoxic effects, also with the ability to directly kill tumor cells. This article reviews the research progress of the role of CD4⁺ T cells in anti-tumor immune response and their application in tumor immunotherapy so as to provide some reference for further development and clinical research of CD4⁺T cells in anti-tumor immunotherapy.