The role of microRNAs (miRNA) in many diseases, including chronic hepatitis, represents an interesting research field. The current work aimed to study the effect of combination therapy (pegylated interferon alpha-2b plus ribavirin) on microRNA-128 (miR-128) and microRNA-296 (miR-296-5p) expression in patients with chronic hepatitis C. Also, we aimed to investigate the potential value of both types of microRNAs in differentiation between responders and nonresponders either in the pre-treatment or post-treatment groups. Sixteen patients with chronic hepatitis C were compared to 10 healthy, age and sex matched controls. Venous blood samples were withdrawn before initiation of combination therapy and 12 weeks later and qPCR was used for gene expression assays. Comparison of pre-treatment group to the control group showed significant miR-128 down-regulation, while miR-296-5p showed a non-significant downregulation. Regarding post-treatment group, there was non-significant upregulation of miR- 128, while miR-296-5p was significantly downregulated compared to either pre-treatment group or the control group. Comparative studies of miR-128 and miR-296-5p in responders versus nonresponders showed non-significant fold change either in the pre- or post-treatment groups. It could be concluded that chronic hepatitis C as well as the combination therapy modulate miR- 128/296 expression. Until now, miRNAs studied were not useful indicators to differentiate between responders and non-responders to combination therapy either in pre- or post-treatment group.