Introduction: Immune effects of vitamin D including its cytokine regulating actions are mediated through the nuclear vitamin D receptor. Genetic polymorphisms affecting the vitamin D receptor FokI gene have been implicated in several immune disordersAim of the study: In this study we assess the effect of FokI gene polymorphism and vitamin D levels on response to treatment in chronic hepatitis C genotype 4.Patients and methods: Blood samples of 50 responders and 50 non- responders to pegylated interferon and ribavirin were tested for the FokI gene polymorphism and serum vitamin D levels. 20 healthy controls were also tested for serum vitamin D levelsResults: Mean baseline vitamin D level was 5.9 ±3.9 and 32.5 ±12.9 ng/ml in HCV patients and controls respectively (P: <0.001). All HCV patients were deficient to vitamin D (<30ng/ml). At the end of treatment serum vitamin D levels remained unchanged in non-responders (7.2 ±2.9 vs 6.5 ±4.8ng/ml, p:0.3), while in responders serum vitamin D levels improved significantly (5.3 ±2.8 vs 65.8 ±16.2ng/ml, p: <0.001). VDR FokI polymorphism (ff or Ff) was detected in 45 (90%) non-responders vs only 20 (40%) responders (p:<0.001). Logistic regression revealed that higher age, alkaline phosphatase and VDR FokI polymorphism were associated with non-response.Conclusion: The FokI VDR polymorphism is independently associated with poor response to therapy in genotype 4 HCV. Analogous to IL28 gene polymorphisms FokI should be incorporated as a predictor of response in the pre-therapeutic assessment of patients.