CD96 is a type I transmembrane protein expressed on the surface of natural killer cells and activated T cells, belonging to the immunoglobulin superfamily. As a crucial inhibitory immune checkpoint receptor, it primarily binds to its ligand CD155 (PVR), transmitting inhibitory signals that negatively regulate the cytotoxicity and cytokine secretion functions of NK cells and T cells. In the tumor microenvironment, the high expression of CD155 on tumor cells continuously activates the CD96 pathway, leading to exhaustion of immune cell function and thereby promoting tumor immune escape. Consequently, CD96 has emerged as a promising novel target in the field of tumor immunotherapy, with specific antagonistic antibodies currently in preclinical and early-stage clinical research.