The aim of this study was to characterize expression of the alpha B-crystallin gene in human hepatocellular carcinomas, to investigate the relationship between expression of this gene and the prognosis of human hepatocellular carcinoma. Real-time polymerase chain reaction, reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to characterize expression of the alpha B-crystallin gene in human hepatocellular carcinoma. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of human hepatocellular carcinoma. We characterized alpha B-crystallin gene expression in human hepatocellular carcinoma. Statistical analysis of hepatocellular carcinoma patients showed that patients expressing alpha B-crystallin have different survival rates relative to those not expressing this gene (P = .041). After 18 months, the survival rate of patients expressing alpha B-crystallin declined, but survival in the alpha B-crystallin-negative group remained stable. COX multi-factor analysis showed that alpha B-crystallin (P = .007) and venous invasion (P = .037) were independent prognosis factors for hepatocellular carcinoma. Expression of the alpha B-crystallin gene, which is related with the transferability and invasive capacity of hepatocellular carcinoma cells, can be used as a prognostic indicator in human hepatocellular carcinomas. It may also be involved in the malignant transformation of hepatocytes.