Single nucleotide polymorphisms (SNPs) in the Interleukin (IL)-28B gene, namely rs12979860, could predict response to pegylated interferon-α-ribavirin (PR) therapy in hepatitis C virus genotype 1 (HCV-1)-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype (CC) was associated with sustained viral response (SVR) to therapy compared with the homozygous T allele genotype (TT) and the heterozygous genotype (CT). In the SVR group, the response rate was statistically significantly higher in CC genotypes (58.6%) compared with CT/TT (20.3%). There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy.