Recently, we have reported that the majority of HBsAg-negative and anti-HCV positive hepetocellular carcinoma (HCC) was found to have HCV-RNA and HBV DNA integration. It is also important to examine the role of hepatitis B virus (HBV) in HBsAg-negative (NB) and anti-HCV negative (NC) HCC in provoking cancer. To elucidate the important role of the previous infection of HBV, and to clarify the relations of HBV genome integration and p53 gene mutation, telomerase activity and genetic instability in liver tissue with HBsAg-negative and anti-HCV negative HCC we analyzed the backgrounds of 34 NE and NC Japanese patients with chronic liver disease (CLD) patients not associated with HCC and 26 NBNC CLD patients with HCC. We examined 6 with NBNC HCC (NBNC-HCC) tumorous tissues (T) and non tumorous tissues (NT), HBV genome integration into host cell genome was detected by PCR. We analyzed p53 mutation by PCR-FSSCP, Telomerase activity by Trap method. Moreover, we checked RER and LOH of chromosomes 2p, 3p and 17p using PCR, and the existence of TTVDNA were examined by PCR, It is postulated that the important role of the previous infection of HBV may have also been proposed for HCC oncogenic progression in NBNC CLD.