Background: Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver and is a deadly and complex cancer mostly associated with inflammation and oxidative stress in hepatic tissue. An essential first-line treatment for advanced HCC is sorafenib which can significantly improve overall survival. However, due to acquired resistance against sorafenib and the heterogeneity of HCC, there is still opportunity for HCC progress. As a result, sorafenib and other medication combinations may work in concert, offering a novel approach to treating HCC. Objectives: This study was aimed to investigate the impact of the combinations of sorafenib and free anthraquinones fraction, containing aloe-emodin, emodin, chrysophanol and physcion, isolated from Rhubarb officinale rhizome on the chemically induced HCC in rats. Material and methods: sixty male albino rats (Rattus Albinus) of average body weight 130±20 g were used in this study. they were divided into 5 groups (n=12/group):  normal control group, diethylnitrosamine (DEN)+ carbon tetrachloride CCL4 induced HCC (HCC group); and 3 treated groups with anthraquinones (Anth group), sorafenib (Sor group), and both (Anth+Sor). Results: The HCC group of rats exhibited the most deteriorated effects, including elevated serum alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), declined antioxidant activity of glutathione peroxidase (GPX); upregulated expression of the genes related anti-apoptosis (survivin), autophagy (beclin 1, Bec1), angiogenesis (vascular endothelial growth factor, VEGF); and downregulated expression of genes related to apoptosis (p21 and p53). After Anth and Sor were administered, all the negative effects caused by HCC were reversed, with the combined group (Anth+Sor) which showed the greatest improvement. Conclusion: It could be concluded that administration of anthraquinone could improve the therapeutic potential of sorafenib on HCC.