ObjectiveTo study the relationship between hepatitis B virus (HBV) mutation at nucleotides 1653T and liver cancer. MethodsOne hundred and nineteen serum samples of HBVinfected patients were collected (All were positive HBV DNA) , 24 ,35, 29, and 31samples were from asymptomatic carriers（ASC）, patients with chronic hepatitis B (CHB), liver cirrhosis (LC) ,and hepatocellular carcinoma (HCC),respectively. Partial fragments of HBV pre C and C gene were amplified by seminested polymerase chain reaction . The PCR products were subjected to direct sequencing and the mutation at 1653T was determined by sequence analysis. HBV genotypes were detected by restriction fragment length polymorphism based on S gene PCR products. ResultsAll samples from 24 ASC were not found mutation at nucleotides 1653T ; 1(2.86%) sample from 35 CHB and 5(17.24%) from 29 LC were found mutation at 1653T; The detection rate of 1653T mutation was not significantly different between CHB and LC（χ2=2.36, P＞0.05）；14(45.16%) samples were found mutation at 1653T in HCC，the mutation at 1653T in HCC was significantly higher than that of LC(χ2=5.40,P<0.05). Of 119 serum samples of HBV, 2 of 51 genotype B and 18 of 58 genotype C were detected mutation at nucleotides 1653T , the other 10 samples couldn’t be determined genotype .The difference in mutation at 1653T between genotype C and B was significant (χ2=11.57, P<0.01).ConclusionHBV 1653T mutation is correlated with HCC, and is more prone to occur in genotype C infection; 1653T mutation can be as predictive risk factors for hepatocarcinogenesis.