CCAAT/enhancer binding protein alpha (C/EBP alpha) and C/EBP beta, liver specific transcription factors, are involved in hepatocyte proliferation and differentiation. The expression level of the C/EBP alpha and C/EBP beta genes were examined between tumor and non-tumorous tissues of the same hepatocellular carcinoma patients with quantitative real-time polymerase chain reactions. The expression of both the C/EBP alpha and C/EBP beta genes was down-regulated in the majority of the tumor specimens compared with corresponding non-tumorous tissues. Patients whose expression of either C/EBP alpha or C/EBP beta was higher in tumors than non-tumorous tissues survived longer than those whose expression was lower in tumors. Higher expression of C/EBP alpha or C/EBP beta in tumors was reversibly correlated with the tumor size and progression of the clinical stage. These data imply that the comparison of C/EBP alpha and C/EBP beta expression between tumors and non-tumorous regions could be a prognostic marker for patients with hepatocellular carcinoma.