Hepatocellular carcinoma (HCC) is one of the most common cancer types with a high prevalence and itis the leading cause of cancer deaths worldwide. This study aimed to investigate the antiproliferative effect of aqueous and ethanol extracts of Origanum majorana leaf on human hepatocellular carcinoma (HepG2) cell line through incubation of various concentrations of origanum majorana extracts with HepG2 and at different time intervals. The effects of aqueous and ethanol extracts of O. majorana L. on HepG2 cell viability, nuclear factor kappa B (NF-kB) gene expression were examined. The results of the cell viability assays showed that aqueous and ethanol extracts exhibited a highly significant inhibitory effect on HepG2 cell proliferation which was evidenced by a reduction in viable cell count. The results were confirmed by microscopical examination of cell morphology. Furthermore, the O. majorana L. extracts suppressed the activity of NF-kB gene expression of HepG2 cells compared to the control.The conclusions from this study suggest that marjoram extracts exhibit anti-proliferative effect against HCC through suppressing the activity of NF-kB gene expression and high antioxidant activity.