Genetic polymorphisms of the LMP/TAP gene coded by the HLA-II region may be associated with outcomes of HBV infection. We conducted a case-control study to test the hypothesis, including a persistent group of 155 patients with chronic hepatitis B and 36 healthy carriers, a recovered group of 165 individuals spontaneously recovered from HBV infection, and an uninfected group of 278 healthy normal controls. Genotypes of eight polymorphisms of the LMP/TAP gene were analysed by PCR–RFLP. A logistic regression model was used to analyse statistical differences in polymorphisms or haplotypes in different groups. Of the eight polymorphisms, two (TAP1 codon 637 and LMP7 codon 145) were observed to have statistically significant association with outcomes of HBV infection (P<0·05). The two-locus haplotype constructed with two such polymorphisms was analysed. The frequencies of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were found to be increased significantly in the persistent group, compared to healthy controls (OR 2·26, 95% CI 1·62–3·15, P<0·001; OR 2·37, 95% CI 1·69–3·32, P<0·001; OR 4·38, 95% CI 1·78–10·77, P=0·001, respectively). The prevalence of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were also significantly higher in the persistent infectious group than in the recovered group (OR 2·68, 95% CI 1·81–3·98, P<0·001; OR 2·40, 95% CI 1·62–3·55, P<0·001; OR 3·03, 95% CI 1·22–7·55, P=0·017, respectively). These findings indicated that genetic polymorphisms of the LMP/TAP gene might be an important factor in determining the outcome of HBV infection.