In our study, p-STAT3 promoted the expression of Anxa2 at the transcription level via binding with the promoter of Anxa2. The specific inhibition of p-STAT3 can significantly reduce the expression of ANXA2, C-CASPASE1, ASC, and GSDMD-N, thereby improving hepatocyte pyroptosis and fibrosis in NASH. This evidence concerns the gene STAT3 and metabolic dysfunction-associated steatohepatitis.