BACKGROUND Our aim was to explore the mechanism of post-transplant organ function decrease induced by brain death (BD) and discover a potential candidate drug for improving the survival and organ function after BD. MATERIAL AND METHODS The microarray data developed from the liver tissues after BD were further analyzed by bioinformatics methods. The differentially expressed genes (DEGs) were computationally predicted and the DEGs that involved biological functions were explored by gene ontology (GO) analysis. The candidate agents that could induce the reverse gene signature were predicted based on the Connectivity Map (CMap) database. RESULTS There were total 1374 DEGs, including 589 up-regulated genes and 785 down-regulated genes. Function analysis showed that DEGs were mainly enriched in biological process-related GO terms, such as regulation of transcription, DNA-dependent, inflammatory response, and regulation of phosphorus metabolic process. The down-regulated genes were significantly enriched in transcription factor activity and transcription regulator activity-related molecular function. The down-regulated GO terms exhibited close interaction with each other. CONCLUSIONS The organ function decrease may be attributed by transcription alteration, inflammation response, and metabolic alteration in liver after BD. Spaglumic acid and halcinonide may be potential drugs for preventing organ damage during the BD process.