Background: The human leukocyte antigen (HLA) system plays critical roles in regulating immune responses to various vaccines. This study aimed to evaluate the association of HLA class II gene polymorphisms and the long-term duration of anti-HBs response in children vaccinated against hepatitis B during infancy. Methods: Totally 297 children 5-7 years after the completion of primary vaccination against hepatitis B in infancy, without booster immunization or natural resolved infection, were enrolled. Of them, 86 children with anti-HBs= 10 mIU/ml were defined as long-term responders. Ten alleles in HLA-DR and -DQ subregions were detected by polymerase chain reaction with sequence-specific primers. Results: The frequency of HLA-DQB1*0401 was 15.1% in the long-term non- or hypo-responder group, relatively higher than 7.6% in the long-term responder group (OR = 2.17, 95% CI 1.01-4.73), however, the difference had no statistical significance after Bonferroni correction (P = 0.470). The frequencies of seven HLA-DRB1 alleles, including (*)01, (*)03, (*)04, (*)07, (*)08, (*)11, and (*)1301/1302, and two HLA-DQB1 alleles, including (*)0201 and (*)0501, were each similarly distributed in the long-term non- or hypo responders and responders respectively. Conclusion: None of the ten HLA class II gene alleles previously reported to be related with short-term antibody response to hepatitis B vaccine is associated with the long-term antibody response after vaccination during infantile. (C) 2017 Elsevier Ltd. All rights reserved.