e22254 Background: Copper metabolism MURR1 domain-containing10(COMMD10), a novel component of FCOMMD protein family, is a protein involved in multiple cellular pathways, including copper homeostasis, NF-κB and HIF signalling. However, its expression and role in HBV-related hepatocellular carcinoma remain unclear. Methods: The expression of COMMD10 was detected in clinical formalin-fixed paraffin-embedded (FFPE) hepatocellular carcinoma tissues by immunohistochemistry with clinicopathological analyses and determined in matched pairs of fresh frozen tissues by Quantitative Real time PCR or Western blot. Results: Immunohistochemistry staining was performed in 129 cases of clinical paraffin-embedded HCC tissues. The staining signal of COMMD10 was mainly observed in adjacent normal livers or cirrhotic livers. Meanwhile,no signals or only weak signals were detected in HCC tissues. Among 129 samples, 94 cases of them (72.9%) exhibited low-expression of COMMD10 (0 to 1+) and high-expression of COMMD10 (2+ to 3+) was found in the other 35 cases (27.1%). The expressions of COMMD10 were significantly lower in HCC tissues than in adjacent normal livers or cirrhotic livers, respectively (Z = 27.038, P = 0.001; Z = 25.047, P = 0.001). COMMD10 expression was strongly correlated with the differentiation(P = 0.041) and serum AFP level in clinic (P = 0.009). From univariate analysis, the significant prognostic factors were COMMD10 expression (P = 0.005), portal vein thrombosis(P = 0.001), differentiation (P = 0.001), dissemination (P = 0.001). Multivariate analysis results showed that COMMD10 expression, portal vein thrombosis, differentiation and dissemination might play a role in predicting the overall survival in HBV-related HCC patients (P = 0.05). Conclusions: In this study we identified COMMD10 downregulation significantly correlated with poor prognosis in HBV-related Hepatocellular carcinoma. COMMD10 status was considered as an independent significant prognostic factor and a possible target for the development of new drugs in HBV-related HCC.