ObjectiveTo investigate the expression and clinical significance of cytochromes b561 (CYB561) in hepatocellular carcinoma (HCC). MethodsThe expression of CYB561 mRNA in HCC tissues and its relationship with prognosis were analyzed by database data. Immunohistochemistry (IHC) was used to detect the expression of CYB561 protein in 61 matched HCC tissues and their adjacent tissues, and the relationship between CYB561 protein expression and clinicopathological features and prognosis of HCC was analyzed. Kaplan-Meier method was used to draw the survival curve and Cox proportional hazard regression model was used to analyze the correlation between the expression of CYB561 protein and the prognosis of HCC. ResultsThe analysis of database data showed that the relative expression of CYB561 mRNA in HCC tissues was higher than that in adjacent tissues (P<0.001). Compared with HCC patients with negative expression of CYB561 mRNA, HCC patients with positive expression of CYB561 mRNA had worse overall survival (OS), relapse-free survival, progression-free survival and disease-free survival (all P<0.05). The results of IHC showed that the positive rates of CYB561 protein in HCC tissues and adjacent tissues were 57.38% (35/61) and 21.31%(13/61), respectively. The former was higher than the latter, with statistical significance (χ2=16.624, P<0.001). Survival analysis showed that the OS of patients with positive expression of CYB561 protein was worse than that of patients with negative expression (P<0.05). Multivariate Cox proportional hazard regression analysis showed that the positive expression of CYB561 protein was a risk factor for postoperative OS in HCC patients [HR=3.308, 95%CI (1.344, 8.144), P=0.009]. ConclusionCYB561 is positively expressed in HCC and suggests a worse survival, and may serve as a potential prognostic biomarker for HCC.