To elucidate the effect of genistein on liver lipid metabolism disorders in laying hens and its potential molecular regulatory mechanisms，180 60-week-old Hy-line Brown laying hens were selected for the experiment.The hens were randomly divided into a control group （CON，fed the basal diet） and a genistein group （GEN，fed the basal diet supplemented with 20 mg/kg genistein），and were fed for 8 weeks.After the feeding period，serum and liver tissue samples were collected to measure serum lipid indicators （TG，TC，LDL-C，HDL-C），liver function indicators （ALT，AST），and inflammatory factors （IL-1β，TNF-α）.Additionally，the activity of liver antioxidant enzymes （SOD） was assessed，liver tissue sections were examined histologically，and transcriptome sequencing along with protein-protein interaction （PPI） network analysis were performed.The results showed that，compared with the CON group，the GEN group exhibited significantly lower serum levels of TG，TC and LDL-C （P<0.05），and significantly higher HDL-C levels （P<0.05）.Histological examination of liver sections revealed a reduction in vacuolar degeneration and lipid droplet deposition.Additionally，serum ALT activity was significantly decreased （P<0.05） in the GEN group，SOD activity in liver tissue was significantly increased （P<0.05），and levels of inflammatory factors IL-1β and TNF-α were significantly reduced （P<0.05）.Transcriptomic analysis revealed that in the GEN group，the expression of genes such as apolipoprotein D （APOD） and fibroblast growth factor 19 （FGF19） was upregulated，whereas the expression of genes such as fatty acid elongase 6 （ELOVL6） and thyroid hormone-responsive protein （THRSP） was downregulated.Furthermore，there was significant enrichment in the fatty acid biosynthesis，PPAR signaling pathway，and primary bile acid biosynthesis pathways.Protein-protein interaction （PPI） network analysis further indicated that ELOVL6 and FGF19 may be key targets through which genistein regulates lipid metabolism.These results suggest that genistein can synergistically enhance antioxidant and anti-inflammatory capabilities by regulating genes and signaling pathways related to lipid metabolism，thereby effectively alleviating lipid deposition in the livers of laying hens during the late laying period.