〔Abstract〕 Erythropoietin-producing hepatoma receptor A2 (EphA2) is a member of the erythropoietin-producing hepatoma (Eph) subfamily of receptor tyrosine kinases. As a critical regulator of cancer development and progression, EphA2 can promote tumor initiation, growth, invasion, metastasis, stemness, and angiogenesis by activating or enhancing the oncogenic signaling pathways. High expression of EphA2 in tumor tissues is closely associated with poor prognosis, thus it is a very promising potential target for cancer treatment. This article reviews the molecular mechanisms by which EphA2 promotes cancer development and progression, aiming to provide clues and theoretical basis for EphA2-targeted cancer treatment.