Background: Liver cirrhosis has emerged as a major cause of global health burden. The vast majority (80-90%) of HCCs develop in a cirrhotic liver. Liver cirrhosis and HCC due to chronic hepatitis C are among the main indications for liver transplantation. The confront in the 21st century is to prevent the need for liver transplantation in cirrhotic patients as much as possible. Due to the unique situation of hepatitis C virus (HCV) in Egypt, being plagued with the highest HCV prevalence in the world, a considerable increase was observed in the proportion of chronic liver disease in Egyptian patients. Liver biopsy has traditionally been the “gold standard" test; it is an invasive procedure with rare but potentially life-threatening complications. These limitations rapidly reduced its use to the sake of developing non-invasive methods as indices and imaging. Alpha fetoprotein (AFP) is seen as the commonest and feasible marker for assessing liver cirrhosis; however, it is not completely reliable because of its low specificity and sensitivity. In early cirrhosis, however, conventional imaging can lead to false-negative diagnosis so other strategies are urgently needed. Currently, lack of robust biomarkers still limits evaluation of hepatic failure and progression in chronic diseases, especially in HCV infection. Aim: the main objective of the present study was to evaluate the significance of a new, non-invasive molecular marker, microRNA-615-5p (miR-615-5p) in circulating blood for diagnosing liver cirrhosis arising from HCV infection. Methods: A total of 50 blood samples were collected; 30 samples from hepatic cirrhotic patients, 10 samples from chronic HCV hepatitis patients and 10 control samples. The level of circulating miRNA-615-5p was detected by RT-qPCR in all samples. Besides, miR-615-5p levels in relation to clinical laboratory parameters were explored. Results: The expression of circulating miR-615-5p was distinctly increased in hepatic cirrhosis with HCV chronic patients compared with control group (mean ± SE: 5.44±0.02, P < 0.01 and 4.9±0.01, P < 0.01, respectively). Receiver Operator Characteristic (ROC) curve analysis revealed much higher specificity and sensitivity for the circulating miR-615-5p in comparison to the traditional AFP. Conclusions: The results showed that miR-615-5p might be a potential molecular biomarker for diagnosing liver cirrhosis, implying that it could be even used as a novel non-invasive molecular biomarker for predicting HCV-related liver cirrhosis.