Abstract: Objective To explore the relationship between CXCL10 and the immune microenvironment in hepatocellular carcinoma (HCC), and its correlation with clinical characteristics, providing a theoretical basis for HCC prognostic marker screening and immune therapy optimization.Methods Based on TCGA and GEO databases, key gene CXCL10 closely related to the immune microenvironment of HCC was selected and verified. The correlations with CXCL10 expression with survival, and immune infiltration were analyzed. Immunohistochemistry and ELISA assay were used to verify the expression of CXCL10 in HCC tissues and plasma. Its correlation with clinical pathological features and inflammatory markers was analyzed.Results CXCL10 was significantly overexpressed in HCC tissues and peripheral plasma (P<0.001), and closely related to tumor stage, pathological grade, tumor size, microvascular invasion, and HBV infection (P<0.05). It was also highly expressed in early-stage patients (P=0.018), suggesting a better prognosis (P=0.021). CXCL10 promoted the infiltration of CD8⁺ T cells and M1 macrophages (P<0.001) to enhance antitumor immunity by mediating antigen processing, NK cell cytotoxicity, and interferon pathways. Its expression was positively correlated with the CALLY index (P<0.001) and negatively correlated with several liver function and inflammation markers (P<0.05).Conclusions CXCL10 is highly expressed in HCC and closely associated with tumor clinical pathological features and prognosis. It plays a role by activating antigen presentation and NK cell cytotoxicity pathways, with potential for HCC diagnosis, prognosis assessment, and immune therapy targeting.