Since the relationship between host factors and response to interferon (IFN) therapy is still a big basal. This study was conducted to : (i) detemine the influence of pegylated IFN vs standard IFN on these cytokines, and (ii) establish the possible relationship between these cytokines and the outcome of treatment. Thirty eight patients were investigated for the serum level of previously mentioned cytokines in a randomized, opened and controlled trial (22 patients treated with pegylated IFN and 16 patients treated with standard IFN). Serum cytokines levels were measured at 0, 1 and 12 months of IFN therapy by (ELISA). Our results indicated that serum levels of TNF-RII, IL-8, sFas, and sFas-L have the potential to be used as non- invasive serological markers for the long- term response to pegylated IFN therapy. Moreover, TNF-RI & RII have the potential to be used for standard IFN treatment.Persistent correlations between sFas and TNF-RII were noted, which may elaborate the possible role clearance with pegylated IFN treatment.