Employing a high-fat diet (HFD)-fed mouse model for in vivo experimentation and palmitic acid (PA)-treated hepatocytes for in vitro analysis, our study extensively explored the pivotal role of the circSOD2/miR-532-3p/TXNIP/NLRP3 axis in NAFLD, offering novel molecular targets for therapeutic strategy development against this condition. Here, TXNIP is linked to metabolic dysfunction-associated steatotic liver disease.