Hepatocellular carcinoma (HCC) is an aggressive malignancy and carries a poor prognosis. Documentation of the wide geographical variation in its incidence has led to clear identification of several risk factors. These include hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in endemic areas. The present study investigated the association of HBV with HCV and cirrhosis, the latter is regarded as a premalignant lesion and underlies most cases with HCC. Serum samples from 94 patients with HCC (n=25) and cirrhosis (n=69) were tested for hepatitis C virus antibody (anti-HCV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and serum alphafetoprotein (AFP). Of the 94 patients, 71 (75.5%) had anti-HCV, 6 (6.4%) were positive to HBsAg, while 64 (68.1%) were positive to anti-HBc. These viral markers were more prevalent among HCC patients, 19 (76.0%) had hepatitis C antibody, 3 (12.0%) were positive to HBsAg and 22 (88.0%) were positive to anti-HBc compared with 52 (75.4%), 3 (4.3%) and 42 (60.9%), respectively in patients with cirrhosis. Regarding serum AFP measurement, 14 (56%) of patients with carcinoma and 35 (50.7%) of patients with cirrhosis demonstrated levels above 7 ng/ml. In patients with cirrhosis, elevated serum AFP and presence of anti-HCV in serum were significantly associated. In conclusion, this study shows that viral hepatitis is strongly associated with the development of cirrhosis and HCC in Egyptian patients. Hepatitis C virus seems to play a predominant role compared with hepatitis B virus.