Plant parts play a crucial function to protect organisms from the toxic/carcinogenic effects of some compounds. The present study was carried out to investigate the protective effects of Graviola aqueous extract (GAE) against carbon tetrachloride (CCl4) which induced hepatic injury in rats. Thirty male albino Wistar rats were divided into five groups: group I was used as controls, group II received daily GAE (300 mg/kg bw) alone orally for six weeks, group III received by IP injection CCl4 in olive oil (50% V/V, 2 ml/kg bw), twice a week for two weeks, group IV, CCl4+GAE (curative group) injected CCl4 twice a week for two weeks then concomitant with GAE (300 mg/kg BW) daily for next four weeks, and group V, GAE+CCl4 (prophylactic group), received GAE, 300 mg/kg/day once daily orally four weeks, then concomitant with CCl4 twice a week for next two weeks. The obtained results showed that the administration of CCl4 caused hepatotoxicity as monitored by the significant (p≤0.05) increase in the levels of hepatic markers enzymes (alanine aminotransferase, ALT, aspartate aminotransferase, AST and alkaline phosphatase, ALP), total bilirubin (TB) and a decrease in hematological parameters such as white blood cell (WBC), red blood cell count (RBC), and blood platelet count (PLT). Also, our results showed that CCl4 caused a significant (p≤0.05) increase in oxidative stress markers (malondialdehyde, MDA, reactive oxygen species, ROS, nitric oxide, NO), pro-inflammatory tumor necrosis factor-alpha (TNF-α,) level, and proapoptotic markers caspase-3, and B-cell lymphoma 2 (BCL-2)-like protein 4 (Bax). Furthermore, a significant (p≤0.05) decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), and an antiapoptotic agent B-cell lymphoma 2 (Bcl-2) was observed in liver tissue. The detected CCl4 effects were normalized by GAE administration, either a prophylactic or curative dose. Besides, GAE reduced the histopathological changes induced by CCl4.In conclusion, GAE was effective in both protecting and enhancing the liver deficits induced by CCl4 through many potential mechanisms including antioxidant, anti-inflammatory, antiapoptotic properties. Therefore, Graviola extracts up to 300 (mg/kg bw) could be considered a promising hepatoprotective supplement but more human clinical trials are also needed to validate the findings of the current research.