Finally, we identified and verified 9 key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18), and we predicted seven potential drugs for multi-organ damage in LPS-induced endotoxemia. This evidence concerns the gene ISG15 and serum lipopolysaccharide activity.