Abstract： Objective To investigate the association between polymorphism of TNFα-308 and mutations of HBV C region in patients with chronic HBV infection. Methods Ninety-five patients with chronic HBV infection were recruited in the study. The single nucleotide polymorphism(SNP) of TNFα-308 Was determined by restriction fragment length polymorphism(RFLP). Mutations of nt1762/1764, nt1896, nt1899, nt1862, as60, aa87 and as97 in HBV C region were detected by direct sequencing after PCR amplification. Mutations of the above points among different genotypes were compared by Fisher's exget test. Results Three different genotypes G/G(63/95, 66.3%), G/A(28/95, 29.5%) and A/A(4/95, 4.2%) were found in TNFα-308 site. The rates of mutations of aa87 and aa97 points in patients with G/G, G/A and A/A genotype were 39.3%(24/61), 11.5%(3/26) and 50.0% (2/4), respectively(F=7.658, P<0.05);while the mutation rates of nt1762/1764, nt1896, nt1864, nt1899 and aa60 were of no statistical significance among different genotypes(F=0.669, 1.542, 1.123, 2.420 and 0.966, P>0.05). Conclusion Compared with G/G genotype, antigenicity of HBV may be more stable in patients with TNFα-308 G/A genotype, which is beneficial to HBV clearance.