Abstract
IFN‑stimulated gene (ISG)20 is a key member of the ISG family, serving a central role in antiviral defense, immune regulation and cell metabolism through its exonuclease activity. ISG20 is markedly dysregulated in various malignancies, including clear cell renal cell carcinoma, glioma, breast cancer and hepatocellular carcinoma, and it is associated with tumor proliferation, metastasis, angiogenesis and immune evasion. Its dual regulatory roles, such as promoting tumor progression via the MMP9/CCND1 signaling axis or enhancing antitumor immunity by activating the IFN‑β pathway, highlight its complex involvement in tumor biology. The present review aimed to summarize the discovery, structural characteristics and physiological functions of ISG20, and its multifaceted roles in tumor development. Moreover, the potential of ISG20 as a novel biomarker, immunoadjuvant and therapeutic target is discussed, offering theoretical insight and translational directions for precision oncology.