Objective:To analyze the expression of tuftelin protein (TUFT1) and its clinical value in hepatocellular carcinoma (HCC)-related liver cancer tissues.Methods:The biological information data of TUFT1 mRNA expression in liver cancer and non-cancer tissues were analyzed from the TCGA and Oncomine database. After the approval of the ethics committee, the self-pairing method was used to collect the postoperative cancer and para-carcinoma tissues of 132 HCC cases hospitalized between January 2009 and December 2014. Tissue microarray and immunohistochemistry (IHC) were used to analyze the expression of TUFT1 in liver tissues. According to IHC staining, liver cancer was divided into high TUFT1 and low/no expression group. Combined with clinical data, the clinicopathological characteristics were statistically analyzed between and within the groups. The 5-year overall survival (OS) and disease-free survival (DFS) was analyzed by correlation analysis.Results:IHC staining showed that TUFT1 in cancer tissue was localized in the cytoplasm and cell membrane, and its positive expression rate was significantly higher in the liver cancer group (87.1%) than the para-carcinoma group (64.4%) ( χ2 = 18.563, P < 0.001). TUFT1 expression intensity in patients with liver cancer was significantly correlated with HBeAg positive ( χ2 = 4.080, P = 0.043), tumor size ( χ2 = 9.388, P = 0.002), vascular invasion ( χ2 = 14.885, P < 0.001), TNM stage ( χ2 = 13.516, P < 0.001) and ascites ( χ2 = 5.940, P = 0.015). TUFT1 high expression was negatively correlated with OS and DFS ( P < 0.001). Conclusion:The overexpression of TUFT1 is closely related to HBV replication, vascular invasion and poor prognosis, and it is expected to become a useful marker for liver cancer diagnosis and prognosis.