Abstract Background: HCV prevention as well as control is based on comprehensive circulation of the virus, valuation of the increasing causes liable for advancement of the HCV and determination of the risk factors involved. Aim of Study: The Study was designed to reveal the gene expression of Signal transducer and activator of transcription 1 (STAT-1), the interferon-a/b  receptor 2 (IFNAR-2) and insulin receptor substrate 2 (IRS-2) in subjects with Hepatitis C, resistant and responding to Interferon Therapy and in healthy control. Material and Methods: This Cross-sectional analytical study included 45 subjects. The subjects were categorized into three groups. Group 1: 15 HVC subjects resistant to interferon therapy Group 2: 15 subjects responding to inter-feron. Group 3: 15 healthy control. Biochemical enzyme activity was measured. Gene expressions were carried out using RT-PCR technique. Results: HCV subjects resistant to interferon therapy showed low expression of STAT1, while subjects responding to interferon therapy showed high level of expression of STAT1 when compared to control and low expression of IFNAR was also seen in subjects resistant to interferon therapy and high expression of IFNAR2 was seen in subjects respond-ing to interferon therapy as compared to control. No expression of IRS-2 was seen in both subjects resistant and responding to interferon therapy. Furthermore, the study revealing no association between STAT1, IFNAR2 and IRS-2 expression and biochemical enzyme levels. Conclusion: Subjects with HCV resistant to interferon therapy illustrated low expression of STAT-1, and also low expression of IFNAR-2 which can be used as a potential indicator of significant liver damage, fibrosis and thus, might prove to be valuable prognostic or diagnostic marker for HCV.