The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). The human WW domain containing E3 ubiquitin protein ligase 1 (WWP1) gene is frequently amplified in prostate and breast cancers, however, its role in cancer has not yet been extensively studied. Especially, the role of WWP1 in HCC has not yet been studied. Firstly, we analyzed the expression of WWP1 in HCC samples. We found that protein levels of WWP1 are higher in most HCC cancerous tissues as compared with their matched adjacent non-tumor tissues. Additionally, the WWP1 mRNA was also amplified in all 7 HCC tissues. Knockdown of the endogenous WWP1 using small interfering RNA further showed that deficiency of WWP1 suppressed cell growth and caused apoptosis in HCC cells. Knocking down WWP1 promoted cleaved caspase3 protein and p53 expression in HCC cells, and caspase3 inhibition could prevent cell apoptosis induced by the knockdown of WWP1. All together these results indicate that protein levels of WWP1 in most HCC tissues are higher than non-tumor tissues, and knockdown of WWP1 inhibits growth and induces apoptosis in HCC cells through the activation of caspase3 and p53. Therefore, WWP1 gene might be a potential molecular target of HCC. (C) 2014 Elsevier Inc. All rights reserved.