To elucidate the pattern of point mutations in BCP/PC region and deletion mutations in PreS region in patients with HBV infection at different clinical stages and to explore their clinical significance. Fang we studied 180 cases of patients with chronic HBV infection. Among them, 13 cases were asymptomatic HBV carriers, 75 cases were chronic hepatitis B, and 62 and 30 cases were HBV-related cirrhosis and hepatocellular carcinoma, respectively. The results showed that the point mutations in the BCP/PC region included nt 1753, nt 1762, nt 1764, nt 1776, nt 1803, nt 1846, nt 1896. nt 1762 (1764) point mutations in HBV carriers, chronic hepatitis B, HBV-related cirrhosis and liver cancer patients were 7.7%, 68%, 72.7% (68%) and 90.9% (81%), respectively. A1762T+G1764A combined mutation accounted for 36%; A1762T, G1764A, G1896A combined mutation accounted for 11%; T1753A/C, A1762T, G1764A, G1896A accounted for 7% of the incidence. Clonogenic sequencing revealed that the BCP region start site A1727G point mutation rate was 72% and 63% in patients with cirrhosis and hepatocellular carcinoma, respectively. more genetic variants were present in HBeAg negative patients (P=0.022), and G1776A and G1896A mutations were independent predictors of HBeAg negativity, P<0.05. BCP region point mutation was not significantly associated with HBeAg negativity. The frequency of Pre-S gene deletion mutations was highest in patients with cirrhosis and liver cancer, and the frequencies of PreS1, PreS2 and PreS1+S2 deletions in patients with liver cancer and cirrhosis were 7.1%, 71.4%, 7.1% and 41.2%, 58.8% and 29.4%, respectively, P < 0.05. It was concluded that A1727G, A1762T, G1764A and A1727G, A1762T, G1764A and A1762T/G1764A combined mutation and PreS deletion are common in patients with HBV-related cirrhosis and hepatocellular carcinoma, and may be risk factors for liver disease progression.