Background: Hepatitis C virus is a serious global health problem affecting more than 170 million patients who are at risk of developing liver cirrhosis and/or hepatocellular carcinoma. Egypt has the highest prevalence of HCV (genotype 4) as about 14.7% of Egyptian populations are positive for HCV antibodies. Aim: To review recent data and patents concerning cytokine polymorphism that affect the likelihood of achieving SVR and can be used as biomarkers for predicting the treatment response to overcome the unnecessary cost, time, and side effects of antiviral therapy for nonresponders. Methods: Data were pooled from 36 studies carried out internationally in which patients with chronic HCV receiving PEG IFN/RBV therapy were evaluated regarding cytokine polymorphism and/or its mRNA expression profile in relation to therapy response. Results and Conclusions: Studies to date have shown that cytokine gene polymorphism plays an important role in the natural clearance of HCV. Most of polymorphisms are in cytokine gene regulatory regions and are consequently involved directly in controlling the transcription rates. Type 1-like cytokines, such as IL-1β, IL-2, IL-6, IL-18, TNF-α, and IFN-γ were up-regulated in chronic HCV infection. The poor response was found to be associated with high producing genotype of IL-10, up-regulation of IL-28B and most of IGS genes, and associated with downregulation of TGF- β, IFN-γ. Good response was noticed to be associated with high level IL-6, IL-8, and certain genotypes of IL-6, IL-12, IFN-γ, TNF-α IFN λ4 and IFN λ3.