Background and study aim: MicroRNAs were evaluated as biomarkers for liver injury in various liver diseases. This study aimed to evaluate the serum miRNA-122 as a potential biomarker for diagnosis and monitoring different stages of disease in chronic hepatitis C patients. Patients and Methods: A case-control study included 45 subjects, divided into three groups: control group, compensated, and decompensated cirrhotic patients groups. All participants were subjected to full history taking, clinical assessment, routine lab investigations, hepatitis B surface antigen, HCV antibodies, HCV-RNA using PCR, and determination of serum expression of miRNA-122 using real-time PCR. Results: The miRNA-122 expression levels among the two groups with liver disease were significantly higher than the control group. Among cirrhotic patients, the expression levels were significantly higher in the compensated subjects compared to the decompensated group. The miRNA-122 levels decreased with the progression of liver disease (from Child-Pugh class A to C) but without significant difference. Patients with ascites had a significantly lower expression of miR-122 compared to those without ascites. Patients with gastrointestinal bleeding and hepatic encephalopathy had statistically insignificant lower expression of miRNA 122 compared to subjects without these complications. As regards all patients groups there were significant positive correlations between miRNA-122 expression and (AST, ALT, albumin, and viral load) and a significant negative correlation as regard INR. Conclusion: Serum miRNA-122 expression levels decreased with the progression of liver disease and at a cutoff value ≤ 2.74 fold change could predict the occurrence of hepatic decompensation. So Serum miRNA-122 seems to be a useful new diagnostic marker in hepatitis C patients with different stages of the disease.