Objective: To investigate the expression of RNF187 in hepatocellular carcinoma (HCC) and its relationship with prognosis. Methods: The mRNA and protein expressions in hepatocellular carcinoma and tumor-adjacent tissues of HCC patients were determined by qRT-PCR and Western blot analysis, and RNF187 expressions in HCC were detected by immunohistochemistry. The relationship of RNF187 expression with clinicopathologic factors and prognosis in HCC patients were analyzed. Results: RNF187 expressed highly in HCC tissues compared with the corresponding adjacent liver tissues both in mRNA and protein level, and significantly higher in HCC tissue from patients with intrahepatic metastases or vascular invasion than those in HCC tissue from patients without intrahepatic metastases and vascular invasion (all P<0.05). The 5-year survival rate of the high expression group was lower than that of the low expression group (P<0.05). Cox regression analysis revealed that high RNF187 expression was independent risk factor for postoperative survival (HR=1.313, 95％ CI=1.128～1.537, P<0.001). Conclusion: High expression of RNF187 in HCC is closely related to tumor prognosis, which may become a new index to evaluate the clinical diagnosis and prognosis of liver cancer.