The antioxidative, anti-inflammatory, anticancer, and hepatoprotective qualities of ginger have been well-established. This research was purposed to evaluate both ginger extract (GE) and ginger nanoparticles (GNPs) potential chemotherapeutic influences in mitigating hepatocellular carcinoma (HCC) induced by carbon tetrachloride (CCl4) and diethylnitrosamine (DEN) in rats. HCC was induced in rats through DEN injection (200 mg/kg b.w./I.P.). Subsequently, after a two-week interval, rats were exposed to three consecutive weekly doses of CCL4 (3 mL/kg b.w. orally), prepared in a 1:1 dilution with corn oil, serving as a carcinogenic promoter. CCL4 and DEN administration were repeated following an additional 5-week interval. Fifteen weeks after HCC induction, oral treatment with GE (300 mg/kg b.w./day) and GNPs (50 mg/kg b.w./day) was initiated and continued for 6 weeks. Twenty-eight rats were divided evenly into four subgroups: G1 (normal control), G2 (DEN/CCL4 induced HCC), G3 (DEN/CCL4+GE), and G4 (DEN/CCL4+GNPs). The results demonstrated a substantial elevation in AST, ALT, and ALP serum activities and a decrease in liver microRNA-29 expression in rats with induced hepatocellular carcinoma. High levels of TGF-β1, FGF, and HGF also pointed to upregulation during the development of HCC. Treatment with GE and GNPs led to a significant reduction in liver marker enzymes and the heightened expression of TGF-β1, FGF2, and HGF, accompanied by an upregulation of microRNA-29 in rats with liver cancer. In conclusion, GE and GNP treatments may serve as chemotherapeutic agents by activating the tumor suppressor microRNA-29 gene and suppressing angiogenesis growth factors in the liver.