Abstract: Telomeric-repeat binding factor 2 (TRF2) as an important telomere binding protein, protects telomere ends and maintains the structural and functional stability and integrity of telomeres by interacting with five other essential core proteins (POT1, TRF1, TIN2, RAP1, and TPP1) to form a complex called shelterin. An increasing number of studies have discovered the abnormal expression of TRF2 in many tumors and that TRF2 is closely related to tumor occurrence, drug resistance, and tumor angiogenesis. Here, we review the latest research findings on the structure and function of TRF2, as well as the role of TRF2 in the occurrence, development, and treatment of tumors. We hope to provide novel perspectives for the prevention and treatment of tumors.