Abstract Background: Hepatic Encephalopathy (HE) is a major complication of liver cirrhosis characterized with neuropsy-chiatric symptoms it's etiology is multifactorial. Aim of Study: Aim of the study serum ammonia, TNF-alfa and IL-6 levels on the degree and outcome of hepatic encephalopathy in Egyptian cirrhotic patients. Patient and Methods: The study included 90 patients with liver cirrhosis complicated with HE (patients group) and 60 cirrhotic patients without HE as control group (group 3), the patients group divided into subgroups according to the grade of encephalopathy from the beginning the study, group A encephalopathy: Grade 1 and 2 and group B encephalopathy: Grade 3 and 4. All patients were followed-up for 7 days, then divided into 2 groups according to the response to treatment; group 1: Complete recovery and group 2: With improper response. Results: There were statistical difference between patients groups (group 1and 2) and control group (group 3) in terms of blood ammonia levels (67.5±22.5, 13±4.8), serum TNF-a  levels (21.6±3.2, 2.3±.2) and mean serum IL-6 (63.9±15.9, 4±1.29) respectively. There were statistical difference between group 1 and group 2 in terms blood ammonia levels (46±12.8, 86.5±30.5), mean serum TNF-a  levels (7.1±2.9, 29.4±13.3) and mean serum IL-6 (19±9.2, 93.9±20.9). Results also, showed statistical significant difference between group 2A and group 2B in terms of blood ammonia level (79.2±20.6, 173.7±38.7), mean serum TNF-a  levels (18.1±5.3, 39.9±14.5) and mean serum IL-6 levels (69.2±11.1, 118.2±13.8). In group 2 there were significant positive correlation between serum TNF with blood ammonia level (r=0.843, p=0.001), serum IL-6 (r=0.732, p=0.001) and between IL-6 and blood ammonia level (r=0.699, p=0.001). Conclusion: There is a strong relation between high blood level of ammonia, TNF alfa, IL-6 and grade and outcome of HE in cirrhotic patients.