Abstract : <p>The present study aims to evaluate the relevance of IFN&lambda;4rs73555604 SNP and ERAP1rs26618 SNPs and response to direct anti-viral drugs among HCV infected Egyptian patients. 100 participants were included in the study (40 HCV infected patients responded to DAA therapy, 40 HCV infected patients who did not respond to DAA and 20 healthy volunteers). Allelic discriminations of IFN&lambda;-4 rs73555604SNP and ERAPrs26618SNP were carried out using step One real-time PCR. Allelic discrimination of IFN&lambda;4rs73555604 and ERAP1rs26618 exhibited significant differences among the studied groups where 75% of non-responders carry IFN&lambda;4rs73555604T allele while 75% of responders carry ERAPrs26618C allele. Calculations of odds ratio revealed that persons carrying T allele of INF&lambda;4rs555604 and ERAPrs26618 have 2.5 and 3.3 folds more odd to be non-responder to DAA therapy, respectively. IFN-&lambda;-4rs73555604 and ERAP-1rs26618 polymorphism could affect HCV response to DAA treatment among HCV infected Egyptian patients. There was a significant association between INF&lambda;4rs555604CC genotype and response to treatment. However, ERAP1rs26618T-allele was associated with resistance to treatment. Odds ratio calculation revealed that persons carrying ERAPrs26618T allele have 3.3 folds more odd to be non-responder to DAA therapy. Both SNP can be used as surrogate markers to assess response to DAA treatment.</p>