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Cancerous inhibitor of protein phosphatase 2A (CIP2A) is highly expressed in hepatocellular carcinoma (HCC) and promotes cell proliferation, cell invasion, and aggressive tumor behavior. However, there have been few studies on the usefulness of CIP2A as an independent prognostic index of HCC. In the current study, the aim was to explore the association between CIP2A expression and prognosis in HCC.The expression of CIP2A and c-MYC was examined by immunohistochemistry in 136 HCC specimens. CIP2A mRNA expression in 27 HCC tissues was also analyzed using quantitative reverse-transcription polymerase chain reaction. The prognostic significance was analyzed by the Kaplan-Meier survival method and log-rank test. Cox regression was adopted for univariate and multivariate analysis of prognostic factors.CIP2A protein was found to be highly expressed in human liver cancer samples (85/136, 62.5%) and correlated with poor survival (P<0.05). The liver cancer tissues examined exhibited much higher levels of CIP2A mRNA compared with their corresponding normal tissues (19/27, 70.3%). Furthermore, CIP2A mRNA levels were correlated with c-MYC mRNA levels. In addition, the highly expressed CIP2A was associated with recurrence (P=0.014) and invasion (P=0.017) of HCC. Patients with high CIP2A expression had both poorer overall survival (OS) and disease-free survival (DFS). On multivariate analysis, the CIP2A status was a significant prognostic factor for OS and DFS (P=0.017, P=0.026, respectively).CIP2A overexpression may be useful as an independent prognostic biomarker for OS and DFS of HCC.