Objective: To explore the expression and clinical significance of chemokine CXCL10 and CXCR3 in hepatocellular carcinoma (HCC).Methods: The expression and prognostic of CXCL10 and CXCR3 in HCC tumor tissues and non-tumor tissues were analyzed in two different publicly available databases the Cancer Genome Atlas (TCGA) and Liver Cancer Institute (LCI). In addition, quantitative real-time PCR (qPCR) was used to detect the mRNA expression of CXCL10 and CXCR3 in 45 HCC cli-nical samples with HBV infection background. Pearson correlation and Spearman rank correlation were used to determine the correlation between the expression level of CXCL10 and CXCR3 in tumor and non-tumor tissues. Results: In TCGA database, the expression of CXCL10 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: 3.379±2.081 vs. 2.213±2.274, P<0.001; paired samples: 3.159±2.267 vs. 2.213±2.274, P=0.018). Similarly in LCI datebase (7.625±1.683 vs. 7.287±1.328, P=0.009). And higher CXCL10 expression was significantly associated with a better prognosis in the patients with HCC both in TCGA and LCI database (P=0.107, P=0.002). In TCGA database, the expression of CXCR3 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: -0.906±1.697 vs. -1.978±1.629, P<0.001; paired samples: -1.329±1.732 vs. -1.978±1.629, P=0.037), while lower in LCI database (3.989±0.339 vs. 4.074±0.309, P=0.003). In both databases, higher CXCR3 expression was significantly associated with a better prognosis in the HCC patients (P=0.004, P=0.014). Furthermore, in TCGA database, the expression level of CXCL10 and CXCR3 was positively correlated both in HCC tumor tissues and matched non-tumor tissues (r=0.584, P<0.001; r=0.776, P<0.001). The qPCR assay showed that the expression of CXCL10 in HBV-related HCC tumor tissues was significantly higher than those in normal liver tissues [0.479(0.223, 1.094) vs. 0.131(0.106, 0.159), P=0.010], and the expression in HBV-related non-tumor tissues was also significantly higher than those in normal liver tissues [0.484(0.241, 0.846) vs. 0.131(0.106, 0.159), P<0.001]. The same was true as CXCR3 [0.011(0.006, 0.019) vs. 0.002(0.001, 0.004), P=0.004; 0.016(0.011, 0.021) vs. 0.002(0.001, 0.004), P<0.001]. However there was no significant difference of CXCL10 and CXCR3 between tumor tissues and matched non-tumor tissues (P=1.000, P=0.374).Conclusion: Expression of CXCL10 was up-regulated in HCC tissues, expression of CXCR3 was down-regulated in HBV-related HCC tissues, and the higher expression of both genes was correlated with better overall survival in HCC patients.