Background &Objectives: Still there is percentage of HCV patients not responding to Direct Acting Antiviral Agents (DAAS). Liver can be greatly affected by changes in gut Microbiome, microbiota. The study was done to evaluate the association between gut microbiome  versus microbiota in HCV patients and the response to DAAS .Subjects and Methods:   Thirty HCV patients  aged  from20-60years old ,both males and femals; group 1 (No=15 of HCV responders and group 2 (No=15 relapser HCV patients) treated by DAAS according to the treatment protocol of the Egyptian National Committee for Control of Viral Hepatitis (NCCVH).Group 3 healthy control subjects (No=15)  . Full history taking, clinical examination and all investigations were done plus stool culture  by Vitek 2and 16srRNA gene amplification and sequencing were done  as per  Clinilab  Maadi ,Cairo .Statistical  analysis were done  after tabulation  of the results ,p<0.05 considered significant. Results: 16SrRNA gene microbiome was of   statistically significant decrease in (6) micrbiota  in non-responders and increased in (2) .Microbiota  compared to responder group ( with P value: ranged from 0.06 to 0.013) Microbiota which increased in non-responder group than responder group ( with P value: ranged  from 0.002 to 0.003).The  number of microbiota by culture is completely defected and different   between the groups compared to  16SrRNA gene  for microbiome.. Conclusion:  Microbiome more accurate  and specific than stool culture for  detection of microbiota