The large yellow croaker (Larimichthys crocea) is an economically important fish farmed along the southeast coasts of China. In recent years, however, hypoxia has caused substantial economic losses in the L. crocea aquaculture industry. At present, the numbers of genes and molecular markers available for the selection and breeding of hypoxia tolerance traits in L. crocea remain very limited, and thus there is an urgent need to conduct breeding studies on the tolerance of this fish to hypoxia. Genome-wide association studies (GWAS) have been widely used to study the genetic basis of economically important traits in aquatic animals, and in this study, we adopted a GWAS approach to genetically characterize hypoxia tolerance in the L. crocea. A total of 1982 fish were subjected to hypoxia experiments, among which 398 individuals characterized by the most sensitive and tolerant phenotypes were genotyped. Following filtering, we obtained a total of 54,224 high-quality single-nucleotide polymorphisms (SNPs), of which four were identified as significant based on mixed linear (MLM) and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (Blink) model analyses. Using these four SNPs, we identified ten candidate genes, including one gene, egln2, directly associated with hypoxia and other involved in important regulatory pathways, such as oxidative stress, ion regulation, and energy metabolism. These findings provide new insights into the genetic basis of hypoxia tolerance in L. crocea and will facilitate future breeding for marker-assisted selection and the breeding of hypoxia-tolerant L. crocea for commercial production.