Background and Aim: Chronic infection with hepatitis C virus (HCV) is a huge problem both globally and at the level of the individual patient. The natural outcome and response to treatment in hepatitis C virus (HCV) infection varies between individuals. Our aim is to detect the Influence of Vitamin D Receptor Gene Polymorphisms((BsmI) and (Fok1) and Vit. D level in the blood of chronic liver disease patients under treatment with interferon. Subject and Methods: Blood samples were taken from 103 patients who are suffering from chronic hepatitis C disease. They were divided into Respoders (n=63)and Non-Responders (n=40)according to their initial response to treatment with normalization of aminotransferases (ALT and AST) levels and clearance of the virus denoted by negative HCV-RNA by PCR after 6 months of receiving treatment. Also 30 blood samples from controls were taken. The following were done: history taking, general examination, liver function tests, hepatitis markers, HCV quantitation by real time PCR , DNA extraction from whole blood, PCR for gene amplification , agarose gel electrophoresis and quantitation of Vit.D level by ELISA. Results: there was significant differences between responders and non responders to interferon therapy of chronic hepatitis C patients before treatment as regards the mean values of Vit D (P = 0.001). There were significant differences in the prevalence of single nucleotide polymorphism (SNP) in the promotor region of Vit. D receptor gene (BsmI) between responders and non responders to interferon therapy of chronic hepatitis C patients as regards (Bb) (p=0.02) .There was no significant differences in the prevalence of single nucleotide polymorphism (SNP) in the promotor region of Vit. D receptor gene (Fok1) between responders and non responders to interferon therapy of and (P=0.43) respectively. Conclusion: Vitamin D Receptor Gene Polymorphisms((BsmI) and Vit.D level in the blood of chronic liver disease patients are predictors of response to combination therapy of HCV.