ObjectiveTo detect the expression of FXYD domain-containing ion transport regulator 6 (FXYD6) protein in hepatocellular carcinoma tissues and the corresponding paracancerous liver tissues, and to explore the clinical significance of FXYD6 protein expression in hepatocellular carcinoma.MethodsEighty hepatocellular carcinoma tissues and the corresponding 40 paracancerous tissues were retrospectively collected in Cangzhou Central Hospital from March 2012 to January 2018, and the expression of FXYD6 protein was examined in these tissues by strept avidin-biotin complex (SABC) immunohistochemistry. We analyzed the relationship between the expression of FXYD6 protein and clinicopathological characteristics of the patients with hepatocellular carcinoma, and the relationship between the expression of the protein and early recurrence or overall survival.ResultsThe positive expression rate of FXYD6 protein was statistically higher in hepatocellular carcinoma tissues than that in the corresponding paracancerous tissues [77.5% (62/80) vs. 40.0% (16/40), P<0.001]. Its expression in hepatocellular carcinoma was not related with gender, age, histological differentiation, tumor maximum diameter, tumor number, AFP concentration in serum, and HBV or HCV infection (P>0.05), but with integrity of tumor capsule, microvascular invasion, and tumor stage (P<0.05). The positive FXYD6 protein expression group had a significantly higher recurrence rate than that of the negative FXYD6 protein expression group [53.2% (33/62) vs. 16.7% (3/18), P=0.006]. However, multivariate analysis results showed that high FXYD6 protein expression was not a risk factor for early relapse (P=0.422). The positive FXYD6 protein expression group had a significantly shorter postoperative survival than the negative FXYD6 expression group ( P=0.043). However, multivariate analysis results showed high FXYD6 protein expression was not a risk factor for overall survival (P=0.754).ConclusionsFXYD6 protein was expressed abnormally in hepatocellular carcinoma tissues, which might be involved in the carcinogenesis and the progression of hepatocellular carcinoma. It might be a poor prognostic factor for patient with hepatocellular carcinoma.