Background: Direct-acting antivirals (DAAs) has seen a significant increase of the count of patients with hepatitis C virus (HCV) clearing their infection. Interferon Lambda Four (IFNL4) polymorphism plays a distinguished role in spontaneous and treatment-output clearance of HCV infection. Aim of this Work: This study aimed to assess IFNL4 polymorphism among hepatitis C Egyptian patients who were exposed to radiation, compared to normal by a polymerase chain reaction with restriction of fragment length polymorphism (PCR-RFLP) technique. Materials and Method: This study included 50 HCV-positive Egyptian patients working in Egyptian Nuclear materials Authority treated with DAAs therapy. According to treatment, they were split into two groups. Group I included 40 patients with sustained viral response (SVR). Group II included 10 patients with no response (nSVR). Fifty healthy people served as controls. Liver function tests, complete blood count, evaluation of viral markers, HCVRNA by PCR, and evaluation for IFNL4 single nucleotide polymorphisms for rs368234815 were performed by PCRRFLP in all patients. Results: Of the 50 patients, 40 (80%) achieved sustained virological response (SVR). Of the 23 patients with rs368234815 TT/TT genotype, 21 (91.3%) achieved SVR, while in 27 patients with non‑ TT/TT genotypes, 19 (70.4%) achieved SVR. The rs368234815 was a powerful predictor of SVR. However, in the present research individuals, the predictive power of this SNP was the same as that of rs12979860 SNP. Conclusion: In Egyptian HCV-positive patients with genotype 4, IFNL4 rs368234815 SNP is an autonomous predictor of SVR to DAAs treatment.