Background: Our study aimed to investigate the associations between Histamine H4 receptor (HRH4) gene polymorphisms (rs77485247, rs74604924, and rs77041280) and oral H1 antihistamine efficacy for the treatment of allergic rhinitis (AR) patients. Methods: A total of 142 AR patients were selected as a case group and 160 healthy individuals were recruited as a control group. Single nucleotide polymorphisms (SNPs) in the HRH4 gene were detected using direct sequencing. Serum immunoglobulin E (IgE), specific IgE, and eosinophil cationic protein (ECP) levels were measured by enzymelinked immunosorbent assay (ELISA). Clinical efficacy was evaluated by the visual analogue scale (VAS). The occurrence of adverse reaction was recorded. Results: There were significant differences in the distribution frequencies of mutant genotype (TA + AA) and A allele of rs77485247, mutant genotype (AT + TT) and T allele of rs74604924, and mutant genotype (AT + TT) and T allele of rs77041280 between the case and control groups. AR patients with mutant genotype (TA + AA) of rs77485247 and AR patients with mutant genotype (AT + TT) of rs77041280 had higher specific IgE, ECP levels, and VAS scores after treatment and lower incidence of adverse reactions and total effective rate than those with TT genotype and those with AA genotype, respectively. However, for rs74604924, there were no differences was found between AR patients with mutant genotype (AT + TT) and those with AA genotype. Conclusion: Our findings provide evidence that HRH4 rs77485247 and rs77041280 polymorphisms may be associated with the risk of AR and the efficacy of H1 antihistamines for the treatment of AR patients. (C) 2016 ARS-AAOA, LLC.