The present study aimed to evaluate the curative role of Terminalia muelleri ethanolic extract (TME) against diethyl nitrosamine (DENA) induced HCC, in addition to evaluate its role as a combined therapy with Doxorubicin (DOX) which is one of the standard chemotherapy. Sixty adult male albino rats were divided into sixteen control rats and forty-four rats injected with DENA to induce HCC. The induction of HCC was manifested through the significant increase in the enzymatic activity of serum aminotransferases (ALT and AST) with sever changes in liver architecture and HCC was confirmed by the significant increase in serum AFP. The progression of HCC was evidenced by the significant increase in serum AFP, decrease in serum albumin levels and increase proliferation of hepatocellular carcinoma in association with significant decrease of caspase-3 immunoreactivity. HCC-induced rats were subjected to the treatment with DOX, TME and the combination of both. Normal rats were divided into control non-treated group and TME administered group. The obtained data proved that, the treatment with TME elicited an efficient curative effect in the treatment of HCC in comparable with DOX towards HCC and the combination of both exerted a more pronounced curative effect than that obtained by the individual treatment. In conclusion TME could be a promising or adjuvant therapy in the treatment of HCC.