This study was designed to investigate the alterations of individual protein kinase C (PKC) isoforms in human liver cancer. Surgical specimens of hepatocellular carcinoma and adjacent normal tissues were extracted into cytosolic and membranous fractions. The level of membrane-bound PKCα in the cancer tissue was significantly lower than that in the adjacent normal tissue and consistent with the change in PKC activity. In addition, there was a significant negative correlation between PKCα and tumor size. In both cytosolic and membrane fractions, levels of PKCδ and PKCζ was significantly higher in the cancer tissue than those in the adjacent normal liver tissue. The alterations in the PKC isoforms signify their roles in the hyperproliferation in liver cancer.