Abstract: Macrophage migration inhibitory factor (MIF) is a classical pro-inflammatory cytokine that plays an important role in the innate and adaptive immune regulation. In recent years, a large number of studies have demonstrated that the expression level of MIF is significantly increased in a variety of tumor tissues and MIF promotes the occurrence and development of tumors. MIF participates in the regulation of tumor growth, metastasis, angiogenesis, as well as induces and maintains the tumor microenvironment. Targeting MIF has been considered as a candidate strategy against cancer. In this review, the structural features, the signaling pathway, the biological functions of MIF are briefly outlined. Moreover, approaches that target MIF in the treatment of cancer are also summarized.