Natural killer cells (NK) as components of the innate immunity substantially contribute to anti-tumor immune responses, NK cell subpopulations can be defined on the basis of the relative expression of CD16 and CD56 markers. Earlier research demonstrated a dramatic reduction in the frequency of peripheral blood CD56dimCD16+ NK subsets in hepatocellular carcinoma (HCC) patients compared with healthy subjects. We aim to assess the relative and absolute counts of natural killer cells subsets in hepatitis C-related HCC among Egyptian patients. Flowcytometric analysis of peripheral blood NK subsets was performed for HCV with HCC patients (n=20) and HCV without HCC patients (n=14) as compared to healthy control subjects (n=152). We found that HCC patients displayed a marked reduction in the relative frequency of peripheral CD56im subsets compared with healthy subjects. Moreover, there was a significant reduction in the absolute counts of CD56dim16+, CD56dim16- and CD56bright. In conclusion, this study demonstrated that the absolute counts of dim and bright NK cell subsets were decreased in different proportions in patients with HCV-related HCC that refers to a possible role for these cells, particularly CD 56 bright cells, in the immune response to HCC. This might aid in developing new therapeutic strategies targeting both NK subsets for HCC.