Innate immunity is thought to contribute to sustained virological response (SVR) to pgylated interferon-?/ribavirin (peg-IFN-?/ribavirin) therapy. Natural killer (NK) cells are implicated in the regulation of a protective immune response in patients chronically infected with HCV. We sought to investigate the level of NK subsets among Egyptian patients with chronic HCV and to analyze the influence of IFN therapy on this level. Samples were collected from chronically infected patients (n= 37) at baseline and from a subset before and after 6 months on peg-IFN-?/ribavirin therapy. NK cells were characterized by flow cytometry. The number of CD3- CD56+ cells was significantly lower in patients with chronic HCV infection before treatment compared to healthy controls, but they increased during IFN therapy. There was a significant increase in the number of CD16+ and CD3- CD56+ cells in patients with sustained virological responses (SVR) during therapy compared to patients are non-responders (NR). Meanwhile, CD56+ cells were significantly increased in patients with chronic HCV infection before treatment compared to healthy controls and decreased during therapy in responders.