Background: MicroRNAs are a class of small non-coding RNA molecules that function through post-transcriptional regulation of gene expression by a process termed RNA interference (RNAi), and that also have to prominence as critical regulators in a wide array of mechanisms of cell physiology. Aim of the work: The study will attempt to evaluate the expression of several microRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C (CHC) at 12 hours after the first injection of pegylated interferon in comparison with healthy  controls. Patients and methods: forty patients with chronic hepatitis C virus infection (CHCV), their age ranged between (20-56) years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, after 12 hours of the first interferon injection, and twenty healthy individuals were included to serve as controls. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of samples for routine laboratory investigations. CBCs and Taqman quantitative RT-PCR for    MicroRNAs expression analysis of miR- 128a, miR 196a,  miR- 196b, miR 296. Results: Our study revealed that the microRNAs had a higher levels of expression in cases of CHCV infection. Conclusion: Ourstudy concluded thatthere's a highly significant increase in expression levels of IFN-induced microRNAs were observed in patients of microRNAs-128a, 196a, 196b, 296. Recommendations: The future use of  miR inhibitors or mimics and / or siRNAs might be useful for the development of  diagnostic and therapeutic strategies aimed at the recovering of protective innate responses in HCV infections.