To assess the role of IL28B rs 12979860 polymorphism in predicting response to treatment in genotype 4 (G4) Egyptian patients, and to evaluate the role of alpha fetoprotein (AFP) in increasing the predictive strength of IL28B rs 12979860 polymorphism to predict response to treatment. One hundred thirty 7 HCV patients were genotyped for IL28B rs 12979860 by polymerase chain reaction--restriction fragment length polymorphism technique. The presence of the C allele of IL28B rs 12979860 was associated with response to treatment, while the T allele was associated with failure of response to treatment. AFP is associated with IL28B rs 12979860 SNP genotypes at cut off 2.68 and 4.5 ng/mL individually. Response rate was 1.3 and 1.6, 3 times higher in CC, CT, and TT respectively in patients below AFP 4.5 ng/mL than in patients above it. IL28B rs 12979860 polymorphism is strongly associated with treatment induced response to treatment. AFP (cut off 4.5 mg/mL) increases the predictive power of IL28B in response to treatment.