Aims: The Single-nucleotide polymorphism in interleukin genes have been reported to be associated with clearance of HCV and sustained virologic response (SVR). Interleukin 28B (IL28B) gene polymorphism is responsible for immune protection against viruses. IL28B gene polymorphism in HCV infection determines the fate of infection toward spontaneous clearance or chronic infection. This study aims to determine that IL28B gene polymorphism is associated with HCV clearance as well as response to interferon treatment in Libyan patient. Methods: Total of 72 patients with chronic HCV infection who received interferon plus ribavirin combination therapy were enrolled in the study. Viral RNA was checked at one, the third and sixth month of treatment. Genotyping of single-nucleotide polymorphism (SNP) rs12979860 of IL-28B gene was performed using DNA isolated from blood plasma. Detection was performed using Applied Biosystem® Real-Time PCR. Results: Twenty-four patients (33%) had CC genotype, 36 (50%) had CT, and 12 (17%) had TT. CC patients obviously had achieved the SVR (91%) more than that of CT/TT (58% and 50%) respectively (P<0.005). This had reported with HCV genotype 1 and HCV genotype 4 infected patients similar to other findings reported by several studies. The studied patients who have infected with HCV genotype 3 had achieved RVR and succeeded to achieve the SVR irrespective of their IL28B genotypes where the relapse there after had reported only with the CC patients. On the other hand, CC/TT (haplotype) patients infected with HCV genotype 2 significantly achieved the RVR that eventually translate to SVR achievement. However, the rate of the RVR for CT patients was indeed lower that consequently translated into a lower SVR rate and higher of the thereafter relapse. IL28B CC genotype was the independent predictive factor for SVR with an (odds ratio [OR] 10.59; (95% confidence interval [CI]: 1.47-76.43; P=0.019). These findings were indeed consistent with several studies using the IL28B with various genotypes as predictive factors for the SVR. Conclusions: The CC patients showed a trend toward higher viral decline more than the CT and TT patients. Therefore, IL28B genotyping may be used as a predictor of IFN-based therapy outcomes, and a strategy for developing personalized treatment of hepatitis C patients in Libya.