In the present study we examined the role of NK cells in liver cirrhosis (LC) and early and advanced stages of hepatocellular carcinoma (HCC). Twenty- four patients with LC secondary to alcoholic liver disease (ALD) and chronic viral hepatitis (CVH), 15 patients with schistosomiasis, and 37 HCC patients participated in this study. Results were compared with control subjects of matched age, sex and race. Natural killer (NK) cytotoxicity showed a nonsignificant difference between LC patients and controls when expressed as number of lytic units (LU) at 20%. Early stage of HCC had only slight depression in NK activity (64.1 LU) as compared to controls (75.8 LU). On the other hand, when HCC reached advanced stage, a significant (p<0.001) depression of NK activity was observed (25.6 LU). NK activity in HCC patients in relation to etiological factors (alcoholism, hepatitis C virus [HCV] and hepatitis B virus [HBV]) of the disease was investigated. HCC patients with and without history of alcoholism showed a nonsignificant difference between the two groups. Similar findings were detected in HCC patients with and without HCB and HBV infections. We conclude that the observed reduction of NK activity in HCC as compared to that in normal subjects and patients with LC, could be one of the critical factors increasing the risk of developing HCC. In addition, serial determinations of NK activities could be an important predictor for the occurrence of HCC in following the clinical course of LC patients.