Protein is an essential component of poultry diets and directly influences growth performance, profitability, and the environment. While the relationship between animal performance and nutrient intake is modulated by gene expression, the transcriptomic mechanisms underlying broiler adaptation to varying dietary protein levels remain underexplored. This research investigated the liver transcriptomic response of broiler chickens fed a reduced crude protein (RCP) diet, aiming to identify differentially expressed genes (DEGs) and metabolic pathways that may underlie protein metabolism and growth. A total of 256 as-hatched Cobb 500 broilers were fed standard starter and grower diets. At the finisher stage (days 19-28), birds were randomly assigned to one of two treatments: normal crude protein (NCP) or RCP diets, with eight replicates per treatment and 16 birds per replicate. The performance results showed no significant difference in weight gain or feed intake between the groups, but the feed conversion ratio was significantly higher (P <
0.05) in RCP-fed birds. Notably, protein utilization efficiency was significantly higher (P <
0.01) in RCP-fed birds than in NCP-fed birds. Transcriptomic analysis of NCP vs RCP revealed 28 DEGs with 9 upregulated and 19 downregulated, including ACSL6, ME1, IGFBP2, HSD3B1, HAO2, MYO1A, and PNPLA3. Functional enrichment analysis revealed significant involvement of DEGs (P <
0.05) in the PPAR signaling pathway and a tendency toward enrichment in the metabolic pathway (P = 0.053). These findings suggest that metabolic adaptations, supported by the DEGs and increased protein utilization, likely enabled RCP-fed birds to perform comparably to those fed the NCP diet. These insights reveal potential transcriptomic markers for optimizing reduced-protein diets in broiler production, aligning the industry goals of balancing productivity with sustainability.