Aquaporin4 (AQP4) has an important role in water homeostasis of human brain and a dysfunction of AQP4 could induce pathological conditions in neuronal activity. The purpose of our work was to evaluate the association of polymorphisms in the AQP4 gene with the risk and the clinical features of migraine. A total of 293 migraineurs and 249 controls were involved in the study. They were genotyped for four single nucleotide polymorphisms (SNPs) of AQP4 gene. No significant difference in the distribution of AQP4 genotypic and allelic frequencies between cases and controls was found. In addition, haplotype analysis did not show any significant difference. Comparison of the clinical features of the disease according to different AQP4 genotypes showed no significant difference. Our data do not support the hypothesis that the AQP4 gene could represent a genetic susceptibility factor for migraine.