In order to investigate the relationship between SNP and Vibrio resistance in immune-related genes of large yellow croaker (Larimichthys crocea), Vibrio anguillarum and Vibrio parahaemolyticus were used to artificially infect large yellow croaker. High-throughput sequencing, screening and analysis of disease-resistant groups before and after infection:(1)17 non-synonymous mutation sites of amino acid were screened from V. anguillarum resistance group.A total of 28 SNPs were screened from the V. parahaemolyticus resistance group.(2)The first-generation sequencing confirmed that the SNP loci was located on the 91196th of chromosome NW_011323507.1 that interleukin-6 receptor gene (IL-6R) was from G changed to C, the proline was mutated to leucine, and the genotype CC frequencies of this site in the V. anguillarum resistance and the control groups were 12.5% and 0, which showed significant difference (P<0.05).(3)And the 35665 base mutation (A-G) of the complement C1q/TNF-related protein 9 (CTRP9) gene on chromosome NW_011323975.1 showed a significant difference in the V. parahaemolyticus susceptibility/resistance groups (P<0.01), the genotype GG frequencies were 37.5% and 0. The results showed that IL-6R-91196-G/C site mutation was associated with V. anguillarum resistance group, and CTRP9-35665-A/G site mutation was associated with large yellow croaker against V. parahaemolyticus.It provides theoretical support for the selection and breeding of large yellow croaker against Vibrio population.