Hepatitis C viral infection is with the highest prevalence rate in Egypt. Direct Acting Antivirals (DAAs) is now the standard of care for HCV infection treatment. Here we assess the predictive value of single-nucleotide polymorphisms (SNP) rs2596542 C/T in chromosome 6 located in MHC class I on the response to DAAs in chronic HCV infected Egyptian patients. This study was performed on 70 Egyptian patients positive for HCV; classified into two groups. Group I: (33 patients) were received combination therapy Sofosbuvir (Sovaldi) 400 mg/day plus Declatasvir 60 mg once daily, Group II: (37 patients) were received Ombitasvir 25 mg, Paritaprevir 150 mg and Ritonavir 100 mg/day plus Ribavirin 15 mg/kg/day for 12 weeks. HCV level by (RT-PCR), MICA single nucleotide polymorphism of rs2596542, ALT, AST, total bilirubin, serum albumin, fasting blood sugar,  HbA1C %, CBC, serum creatinine, AFP were performed in all volunteer patients. Results showed that group II responded with 100% in CT- SNP genotype. However both CC and TT- SNP genotypes responded with 83.33% and 91.67% respectively. There was no observed significant association between SNP rs2596542 C/T and all clinical parameters except AFP that give positive significant correlation in the CC genotype.