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Antihistamines are the first-line treatment for chronic urticaria (CU). However, some CU patients are relatively refractory to antihistamines. The mechanism underlying the interindividual variation is still unknown. The α-chain of the high-affinity IgE receptor is crucial to the IgE-mediated allergic response. The present study is to investigate whether FCER1A polymorphisms are associated with the risk of CSU, and to determine whether these polymorphisms influence the therapeutic efficacy of nonsedating H1-antihistamines. 191 CSU patients treated by nonsedating H1-antihistamines monotherapy (including desloratadine, mizolastine or fexofenadine) were prospectively enrolled in this study. The response to antihistamines monotherapy was assessed by urticaria activity score (UAS7) after 4 weeks of treatment. FCER1A rs2298805, rs10908703 and rs2494262 genotypes were determined by Sequenom Mass Array technology or direct sequencing. There was significant difference in the allele frequency of rs2298805A between CSU patients and 177 healthy subjects (5.3 vs 10.2 %, P = 0.012, OR = 0.491, 95 % CI 0.278-0.865), and also significant difference in the allele frequency of rs2298805A between effective and ineffective groups (7.5 vs 1.0 %, P = 0.015, OR = 8.328, 95 %CI 1.1-63.039). In addition, rs2298805 polymorphism was significantly associated with total serum IgE concentrations (P = 0.011). There were no differences in the rs10908703 and rs2494262 either between CSU patients and healthy controls, or between effective and ineffective groups. These data suggest that rs2298805 might be associated with risk for CSU and the therapeutic efficacy of nonsedating H1-antihistamines in Chinese patients with CSU.