Background Although the precise mechanisms underlying the efficacy of allergen-specific immunotherapy (AIT) are not clear, some evidence suggests that this may be linked to polymorphisms in HLA-II gene. We aimed to investigate the correlation between HLA-II gene polymorphisms and house dust mite (HDM)-specific immunotherapy efficacy, and evaluate specific polymorphisms as potential biomarkers in allergic rhinitis (AR) patients who would benefit most from AIT. Methods Fifty-one Han Chinese patients with AR receiving HDM AIT were recruited. Genomic DNA was extracted from venous blood samples and genotyped for HLA-DRB1 and HAL-DQB1 alleles using the polymerase chain reaction sequence-based genotyping method. Nasal and eye symptoms were investigated based on visual analogue scale and rhinoconjunctivitis quality of life. Results Allele DRB1*04:06; DRB1*14:05 showed a positive correlation with improvements in nasal blockage, nasal itching, eye itching, and activities. Similarly, DQB1*03:02:01; DQB1*05:03: 01 was positively correlated with improvements in nose blocking, nasal itching, eye itching, behavioral problems, and nasal symptoms scores; and DRB1*03:01; DRB1*04:06 positively correlated with nasal symptoms scores. In contrast, DRB1*07:01:01; DRB1*11:01 was negatively correlated with non-pollen symptoms, behavioral problems, and nasal symptoms. Conclusion HLA-DRB1 and HLA-DQB1 gene polymorphism are associated with AIT efficacy in HDM-sensitive Chinese patients with AR, of which DRB1*03:01; DRB1*04:06 and DQB1*03:02:01; DQB1*05:03:01 may be useful biomarkers of AR patient candidacy for effective AIT.