The antioxidative, anti-inflammatory, anticancer, and hepatoprotective qualities of ginger have been well-established. This research 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 (200mg/kg b.w/I. P). Subsequently, after a two-week interval, rats were exposed to three consecutive weekly doses of CCL4 (3ml/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 (300mg/kg b.w/day) and GNPs (50mg/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, along with a decrease in liver microRNA-29 expression in rats with induced hepatocellular carcinoma. Furthermore, elevated levels of TGF-β1, FGF, and HGF suggested upregulation in the context of HCC induction. 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 GNPs treatment may serve as chemopreventive and chemotherapeutic agents by activating the tumor suppressor microRNA-29 gene and suppressing angiogenesis growth factors in the liver.