CD47 belongs to immunoglobulin superfamily and is widely expressed on the surface of cell membrane, while another transmembrane protein SIRPα is restricted to the surface of macrophages, dendritic cells, and nerve cells. As a cell surface receptor and ligand, respectively, CD47 and SIRPα interact to regulate cell migration and phagocytic activity, and maintain immune homeostasis. In recent years, studies have found that immunoglobulin superfamily CD47 is overexpressed widely across tumor types, and CD47 plays an important role in suppressing phagocytes activity through binding to the transmembrane protein SIRPα in phagocytic cells. Therefore, targeting CD47 may be a novel strategy for cancer immunotherapy, and a variety of anti-CD47 antibodies have appeared, such as humanized 5F9 antibody, B6H12 antibody, ZF1 antibody, and so on. This review mainly describes the research history of CD47-SIRPα and focuses on macrophage-mediated CD47-SIRPα immunotherapy of tumors.