Diverse cytokines and their receptors on immune cells constitute a highly complex network in the immune system. Some therapeutic cytokines and their derivatives have been approved for cancer treatment. IL-15 is an immune-regulating cytokine with multiple functions, among which the function of activating the immunity of cancer patients has great potential in cancer immunotherapy. In this review, we introduce the functions of IL-15 and discuss its role in regulating the immune system in different immune cells. Meanwhile, we will address the applications of IL-15 agonists in cancer immunotherapy and provide prospects for the next generation of therapeutic designs. Although many challenges remain, IL-15 agonists offer a new therapeutic option in the future direction of cancer immunotherapy.