In previous study, the 150-ku oxygen-regulated protein (ORP150) was identified as a candidate glycoprotein related to hepatocellular carcinoma. In order to further validate the expression level of ORP150 in hepatocellular carcinoma, protein expression was determined by Western blot and cell immunochemistry, and messenger RNA (mRNA) expression was detected by quantitative real-time polymerase chain reaction. The effect of ORP150 on apoptosis and invasive potential of hepatocellular carcinoma cells was evaluated using the small interference RNA (siRNA) technique. Both the protein and mRNA expression levels of ORP150 were significantly upregulated in hepatocellular carcinoma cell lines compared with a non-tumor human liver cell line. After transfection with the specific siRNA of ORP150, significantly greater apoptosis of hepatocellular carcinoma cells was induced compared with untransfected cells. However, no significant effect on invasive potential was found. Overexpression of ORP150 was associated with hepatocellular carcinoma, and ORP150 might promote the proliferation of hepatocellular carcinoma cells by inhibiting apoptosis. ORP150 could be a potential therapeutic target for hepatocellular carcinoma.