The present study was designed to examine the ability of N-acetylcysteine (NAC) to attenuate Aspartame as a synthetic sweetener (ASP)-induced hepatotoxicity in adult albino rats. Forty adult male rats, weighing 150-170 g, were randomly divided into four groups as follows: first group was given distilled water and served as control group I, Group II: received aspartame (ASP) dissolved in distilled water in a dose of 500 mg /kg. b.wt./day, Group III: received NAC dissolved in distilled water in a dose of 600 mg /kg b.wt./day, and Group IV: Rats received NAC dissolved in distilled water in a dose of 600 mg /kg b.wt./day and aspartame (ASP). Administration of ASP at a dose level of500 mg/kg b.wt. to rats for 42 days significantly elevated the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyltransferase( GGT), tumor necrosis factor (TNF-α) and hepatic alphafetoprotein (AFP) activity which indicate injury to the liver function. Also, total cholesterol, triglycerides and low-density lipoprotein (LDL) increased significantly. On the other hand ASP decreased serum protein, albumin, high-density lipoprotein (HDL) and liver glutathione (GSH) and superoxide dismutase (SOD).These results reflects that ASP intoxication induced marked alterations in liver functions and caused liver atrophy. NAC (600 mg/kg b.wt.) which administered 1h before ASP ameliorated the hepatotoxicity induced by ASP. This was evidenced by a significant reduction in serum ALT, AST, GGT, TNF-α and hepatic AFP activity and a significant restoration in serum protein, albumin, HDL, GSH and SOD. These results indicate that administration of N-acetylcysteine has a strong potential effect against Aspartame-induced damage to liver. This reflects the beneficial role of N-acetylcysteine in treatment of liver injury.