The oyster is the seawater shellfish with the largest production worldwide and strong cadmium (Cd) enrichment and tolerance. Cadmium is transmitted throughout the food chain and can cause serious damage to humans. With industrialization, the accumulative accumulation of Cd in many areas has become an important food safety issue. Genetic improvement of Cd accumulation traits is an important way to reduce Cd content. However, the current genetic mechanisms underlying Cd accumulation in oysters are very limited. Therefore, 1,452,168 single-nucleotide polymorphisms (SNPs) in Fujian oysters were used for the genome-wide association (GWAS) analysis of Cd accumulation traits in this study. The results revealed that 141 SNPs were significantly associated with Cd accumulation traits, 131 of which were concentrated in the 1.28–9.76 Mb range of Chr.3. After Fst selection signal detection and localization, genes such as ZIP1, ZIP3, Slc46a1, and Slc46a3 in this range may be involved in regulating Cd accumulation in Fujian oysters. The coding regions of ZIP1 and ZIP3 were analyzed in another culture population, and six SNPs were found to be significantly correlated with Cd accumulation (P < 0.05), of which five SNP sites had missense mutations, nine haplotypes were formed, and the Cd accumulation of the H6 (ATC) haplotype was significantly lower than that of the other eight haplotypes. In this study, we identified key genes involved in regulating Cd accumulation in Fujian oysters, and related molecular markers can be used for genetic improvement of low Cd accumulation traits. •Genome-wide association (GWAS) analysis localized 141 SNPs significantly associated with cadmium(Cd) accumulation traits, 131 of which were concentrated in the 1.28–9.76 Mb range of Chr. 3.•Through GWAS and fixation indices(Fst) selective signal detection and localization, genes such as ZIP1, ZIP3, Slc46a1 and Slc46a3 may be involved in regulating Cd accumulation in Fujian oysters.•The polymorphism of ZIP1 and ZIP3 were significantly associated with Cd accumulation, in a new population, and low accumulation haplotypes were constructed which woule be used in the breeding.