Background: The exact identification of liver fibrosis is mandatory for customizing therapy and controlling complications. The aim of the current study is to measure the ability to circulate miRNAs; in the diagnosis of hepatic fibrosis.Methods: Routine laboratory, liver biopsy, and histopathological investigations were done on seventy HCV patients. In addition, estimation of HCV-RNA, serum micro RNA (miRNA)-122, 221, 192, 224, 375, and 885 were done by PCR. To assess the ability of each miRNA, the area under the receiver operating characteristics (AUC) curves were plotted. Significant miRNA were analyzed by linear regression analysis in a stepwise pattern to develop a score for pointing out significant fibrosis. Moreover, the following scores were calculated: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), aspartate to platelet ratio index (APRI), FIB-4 score, Hui index, Fibrosis Index (FI), Fibro-Q, Fibro-Alfa Biotechnology Research Center (BRC) score, and Gotebörg University Cirrhosis Index (GUCI).Results: Patients with significant and advanced fibrosis have significantly lower miR-122. MiR-122, FIB4, total bilirubin, and miR-855 proved to be independent predictors of significant fibrosis in univariate analysis. A novel score; Cairo University Fibrosis Index (CUFI) based on microRNA 122, FIB4, bilirubin, and microRNA 855 were formulated for the identification of significant liver fibrosis. The AUC of the score, for predicting significant and advanced hepatic fibrosis was 0.85 and 0.81. This AUC was higher than those of other common fibrosis scores.Conclusion: Cairo University Fibrosis Index proved to be better than other existing scores in assessing fibrosis in chronic hepatitis C (CHC) patients.