Recently there have been several reports that precore mutation is related to progression of hepatitis B. It has been reported that the precore mutation from G to A at site 1896 has been found in the HCC tisses, thus it is considered that this mutation is involved in hepatocarcinogenesis. The aim of this study is to investigate the correlation between precore mutation and progression to HCC. Methods One hundred and five sera samples taken from 65 patients with HCC related to HBV were examined. Subjects were classified into two groups: group I, HBsAg(+)HCV Ab(-); group II, HBsAg(+)HCV Ab(+). Group I was further divided into three subgroups, Ia with HBeAg(+) HBeAb(-), Ib with HBeAg(-)HBeAb(-) and Ic with HBeAg(-)HBeAb (+). Precore mutant was detected by nested PCR-MSSA(Mutation Site Specific Assay). In some cases, mutated and wild precore HBV-DNA were evaluated quantitatively. Results In the group Ia, age on diagnosis of HCC in patients with mutant(+) was significantly younger than that with mutant(-), and increase in mutation seemed to be accompanied by progression to HCC in some cases. Conclusion Our results suggest that increase in HBV-DNA precore mutation is likely to be correlated with progression to HCC, in chronic liver disease related to HBV.