The genomic sequences of hepcidin in Megalobrama amblycephala were obtained from public database to study the association between the hepcidin gene polymorphism and disease resistance trait. Aeromonas hydrophila challenge experiment was used to distinguish susceptible and disease resistant M. amblycephala individuals.The single nucleotide polymorphisms (SNP) of the hepcidin gene in M. amblycephala were screened with PCR and DNA sequencing. Highresolution melting (HRM) were used for SNP genotyping. Two SNPs of the hepcidin gene were screened,one of which was located in the intron region and the other was located in the 3′untranslated region. The results of statistical analyses showed that the genotype and allele frequencies of SNP (A/G) located at 3 371 bp was extremely significant different (P<0.01) and SNP (A/G) located at 217 bp was significant different (P<0.05) between the susceptible and resistant group. It is indicated that the polymorphism of hepcidin gene was significantly associated with bacterial septicemia resistance.