Abstract: Macrophage migration inhibitory factor (MIF) is an important cytokine with dual pro-inflammatory and pro-carcinogenic roles. Aberrant expression of MIF can mediate abnormal activation of multiple signaling pathways and cause the occurrence of hepatocellular carcinoma (HCC), and its mechanisms involve processes such as cell proliferation and migration, regulation of apoptosis and autophagy, and neovascularization. Currently, the clinical treatments for patients with advanced HCC mainly rely on interventional therapy and multi-targeted molecular drugs, but the efficacy is relatively limited. Therefore, finding new therapeutic targets and developing novel anti-HCC drugs are the hot topics in the field of liver cancer treatment currently. This paper reviewed the specific mechanisms on occurrence and malignant progression of MIF-induced HCC as well as its potential as a therapeutic target for HCC, with the aim of providing references for the treatment of HCC.