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Jian-yao Chen,1 Li-ping Liu,2 Jiang-feng Xu3 1Department of Hepatobiliary Surgery, Shaoxing Second Hospital, Shaoxing, 2Department of Surgery, Zhuzhou Clinical Institute, Central South University School of Medicine, Zhuzhou, 3Department of Surgery, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China Abstract: RING domain AP-1 coactivator-1 (RACO-1) is a coactivator that links c-Jun to growth factor signaling and is essential for AP-1 function. This study aimed to investigate the expression and clinical significance of RACO-1 protein in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in China. A total of 136 tissue samples of HBV-related HCC were detected by immunohistochemistry (including 76 patients in training cohort and 60 patients in validation cohort). Correlation between RACO-1 expression and clinicopathologic features of HBV-related HCC was analyzed in both the cohorts. RACO-1 expression was significantly higher in HBV-related HCC tissues than in adjacent non-tumor liver tissues. All the patients were divided into two groups: the low expression group and the high expression group. RACO-1 expression was significantly related to vascular invasion (P=0.021), tumor numbers (P=0.046), International Union for Cancer Control/American Joint Committee on Cancer stage (P=0.006), cirrhosis (P=0.046), capsular (P=0.039), and Barcelona Clinic Liver Cancer stage (P=0.041) in training cohort. The validation cohort showed the same results. The high RACO-1 expression was the independent prognostic factor for HBV-related HCC patients in both training cohort and validation cohort. Our data implicate RACO-1 as a novel prognostic marker and a potential therapeutic target for HBV-related HCC. Keywords: RACO-1, hepatitis B, hepatocellular carcinoma, prognosis, BCLC stage, vascular invasion, cirrhosis, UICC/AJCC stage