Our results unraveled that U50448H could downregulate the C and N terminals of GSDMD, NLRP3, ASC, pro-caspase-1, and pro-IL-1β, as well as block cell pyroptosis, indicating the repressive effects of U50448H on NLRP3 inflammasome-induced cell pyroptosis during ALI secondary to CPB. The gene discussed is CASP1; the disease is acute respiratory distress syndrome.