Leopard coral grouper, Plectropomus leopardus with gorgeous body color and rich nutritional value, which is favored by consumers and has high economic value and breeding value. Growth trait is one of the most important economic traits of fish, and its improvement has contributed to the development of aquaculture industry. However, there has been less research related to the growth properties of the leopard coral grouper. Thus, two strategies of genome-wide association study (GWAS) and RNA-seq were used for five growth traits in 307 leopard coral groupers. We identified 12 significant and 4 suggestive SNPs located predominantly on 23 chromosomes associated with growth traits. Within the 50 kb window of significant and suggestive SNPs, 12 growth-related genes candidates were detected, four of which were located in exon regions, corresponding to the genes zgc:63572, coro2a, btn1a1 and per2, respectively. Interestingly, SNP 23: 17993215 for per2 and SNP 23: 19213238 for btn1a1 occur as non-synonymous mutations in the exon. At the same time, we performed RNA-seq on both the high- and low-weight groups in 6 leopard coral groupers. The results show that 549 differentially expression genes (DEGs) were obtained, DEGs significant enrichment in fatty acid metabolism, amino acid metabolism and other metabolic pathways by GO (Gene Ontology) enrichment and KEGG pathway analysis. Finally, the per2 and acadvl were identified by GWAS and RNA-seq, which play an important role in locomotor activity and metabolism. Our findings could improve the mapping efficiency of leopard coral grouper growth candidate genes, which will provide a theoretical basis for molecular assisted breeding of leopard coral grouper.