Climate change has numerous effects on poultry that result in welfare concerns and economic losses in agricultural industries. However, the mechanisms underlying the acclimation to heat stress in poultry have not been comprehensively defined. Therefore, identifying associated patterns of gene regulation and understanding the molecular mechanisms of acclimation to a warmer environment will provide insights into the acclimation system of broiler chickens. We profiled differentially expressed genes (DEGs) associated with differences in growth performance under heat stress conditions in the liver tissues of broilers based on RNA sequencing data. The DEGs were identified by comparison to the gene expression levels of broilers exhibiting average growth at 28 d of age (D28A) and D36A relative to those at D21A. In D36A, 507 and 312 DEGs were up- and downregulated, respectively, whereas 400 and 156 DEGs were up- and downregulated in D28A, respectively. Pathway enrichment analysis further revealed that "fatty acid degradation" and "heat shock protein expression" were upregulated in broilers exhibiting a higher growth and weight, whereas "cell cycle arrest" and "amino acid metabolism" were downregulated. Transcriptome profiling revealed that the acclimatized group supplied fat and energy from the liver to tissues through the breakdown of fatty acids. Furthermore, homeostasis was maintained via heat shock proteins and antioxidant enzymes. The characterized candidate genes and mechanisms associated with the response to heat stress might serve as a foundation for improving the ability of broilers to acclimatize under heat stress conditions.