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In various genome-wide correlation studies, interleukin <i>(IL)28B</i> gene polymorphism has been strongly correlated with both the therapeutic and spontaneous mediated clearance of hepatitis C virus (HCV). Therefore, this study aimed to evaluate the genotype and allele frequency distributions of <i>IL28B (rs12979860)</i> in patients with chronic hepatitis C and assess the <i>IL28B</i> polymorphisms as predictors of sustained virological response to SOF-based therapy for HCV in Egyptian patients. This retrospective case-control study was conducted on 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and responded to treatment with SVR12 (the responder group) as a control group, and 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and did not respond to treatment and failed to achieve SVR12 (the non-responder group) as a case group. The CC genotype frequency of <i>IL-28B (rs12979860)</i> was greater in the responder group (51.9%). In contrast, the TT genotype frequency was higher in the non-responder group (48.1%) (<i>p</i> < 0.001), and the T allele significantly increased the risk of non-responses by 3.13 fold. Therefore <i>IL-28B (rs12979860)</i> SNP could be used as a genetic predictor of sustained virological response to SOF+DCV ± RBV-based HCV treatment in Egyptian patients.