Hepatitis B and C viruses (HBV and HCV) have been associated with hepatocellular carcinoma (HCC). Recently, a novel DNA virus was isolated from a patient with posttransfusion hepatitis of unknown etiology and designated TT virus (TTV). To examine whether this virus is associated with HCC, we investigated sera from 82 Egyptian patients with histopathologically-diagnosed HCC. All subjects underwent serological investigations for detection of hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HbcAb) and anti-HCV. Detection of TTV-DNA was performed by semi-nested polymerase chain reaction (PCR) using TTV-specific primers. TTV-DNA was detected in 28% of the patients. Age, gender, risk factors and biochemical liver functions did not significantly differ between TTV-DNA positive and negative patients. TTV was detected in 27.1% of patients with HCV-HCC, 25% of HBV-HCC, 66.7% of dual HCV and HBV infection and 40% of those with non-B, non-C-HCC (NBNC-HCC). It is concluded that, in this the cohort of Egyptian patients with HCC, TTV infection is common and is not associated with HCV, HBV, NBNC-HCC, history of schistosomiasis or blood transfusion.