Introduction Prostate cancer (PCa), a kind of heterogeneous malignancy, is the most common cancer and the second most common cause of cancer-related mortality among men in the United States, with 174,650 new cases and 31,620 deaths estimated in 2019.1 Regulated by a huge variety of intrinsic and microenvironmental factors, tumor development and malignancy are multifactorial result.2,3 The microenvironmental mediator has become a promising target for PCa treatment.4 Notably, the chemokines, as microenvironmental mediators, are an important messenger mediating the development of PCa.4 For example, CCL5, the abundant chemokine derived from tumor-associated macrophages, can promote PCa metastasis.5 Increased levels of CCL5 in tissues or blood are positively associated with the poor prognosis and advanced clinicopathological characteristics of PCa.5 Accumulating evidences suggest that targeting the CCL5/CCR5 axis can be viewed as an effective antitumor strategy for PCa treatment.5 At present, the antagonists of this axis associated with PCa are cenicriviroc, maraviroc, anibamine and DT-13. These antagonists can exert valid antitumor effects on PCa. Herein, we review the crucial role of CCL5 in promoting the development of PCa and currently available antagonists that target the CCL5/CCR5 axis for PCa treatment.