Objective In order to explore the expression of CENPU in hepatocellular carcinoma (HCC) tissues and its correlation with the prognosis and clinicopathological characteristics of HCC patients. Methods The HCC data set was collected from the Cancer Genome Atlas (TCGA) database, the cenpu mRNA expression profile and prognosis data were downloaded, the expression of cenpu mRNA in 50 normal liver tissues and 371 HCC tissues were compared, and the correlation between mRNA expression and prognosis was analyzed. Paraffin tissue samples of 80 HCC patients in the first hospital of Lanzhou University from 2010 to 2012 were collected. The protein expression level of cenpu in cancer tissues was detected by immunohistochemical method, and the correlation between cenpu and clinicopathological features was analyzed.Results Patients with high CENPU expression have a poor prognosis (P=0.025). The results of immunohistochemistry showed that CENPU protein in HCC tissue can be used as an independent prognostic factor for HCC patients(P=0.023). Conclusion The high expression of CENPU in HCC may be involved in the carcinogenesis and progression of hepatocytes, and may be a poor prognostic factor for HCC patients.