Objective To evaluate the frequencies and risk of HBV mutations in basic core promoter (BCP) region in HBV-related liver diseases. Methods This case-control study enrolled a total of 2,093 cases, including asymptomatic HBV carriers (ASC), chronic hepatitis B (CHB) patients, liver cirrhosis (LC) patients and hepatocellular carcinoma (HCC) patients. HBV mutations were detected by DNA sequencing method. The association of HBV mutations with the risks of CHB, LC, and HCC was evaluated by non-conditional Logistic regression model adjusted for age and sex as compared to ASCs. Results The frequencies of all the HBV mutations, except for T1768A mutation, in the HCC patients were higher than 30%; while all the HBV mutations frequencies were lower than 30% in ASCs. The frequencies of all the 7 HBV mutations gradually increased in ASCs, CHB, LC, and HCC groups in order (P_trend<0.001). The adjusted odds ratios (AOR) of all the HBV mutations, except for T1768A, were gradually increased in the CHB patients, LC patients, and HCC patients in order compared to ASCs. It was found that A1762T/G1764A was associated with HCC (AOR=13.91; 95%CI=9.66-20.03). The cumulative frequency of HBV mutations in the BCP region gradually increased with progression of hepatitis B-related diseases (P_trend<0.001). Conclusion HBV mutation frequencies in the BCP region gradually accumulate during the progression HBV-related liver diseases, which finally leads to end-stage liver diseases. These HBV mutations can be used for early prediction of HBV-related end-stage liver disease.