BACKGROUND: Currently, the role of p53-induced RING-H2 protein (PIRH2) in the development of hepatocellular carcinoma (HCC) remains unknown. The objective of this retrospective study was to investigate the expression of PIRH2 and its relation to prognosis in patients with HCC after hepatic resection. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR, and Western blot analyses were used to detect expression levels of PIRH2 in 30 samples of HCC tissue and paracarcinomatous liver tissue (PCLT) and in 5 samples of normal liver tissue (NL). In addition, immunohistochemical analysis was performed on 122 HCC specimens and follow-up information data from those patients were reviewed. RESULTS: Both messenger RNA and protein expression levels of PIRH2 were elevated significantly in HCC tissues compared with PCLT and NL tissues. The increased PIRH2 expression was correlated with vein invasion, Edmondson-Steiner grade, TNM stage, and multiple tumor nodes (P<.05). It is noteworthy that the patients with HCC who had high PIRH2 expression had shorter overall survival and diseasefree survival than the patients who had low PIRH2 expression (median survival, 280 days vs 372 days; P = .0002; median disease-free survival, 220 days vs 310 days; P = .0016). Multivariate Cox regression analysis revealed that high PIRH2 expression was an independent prognostic factor for patients with HCC (relative risk, 1.792; P = .009). CONCLUSIONS: The current data revealed that increased expression of PIRH2 was correlated with poor survival in patients with HCC, indicating that PIRH2 is a novel prognostic marker for HCC. © 2009 American Cancer Society.