In view of the positive effects of Nifu on biological processes and STAT3, as well as the important role of this signaling molecule in NAFLD and hepatic insulin resistance, we assessed whether Nifu could attenuate hepatic glycolipid metabolic disorders and mitigate liver inflammation by inhibiting the STAT3 cascade using a palmitic acid (PA)-induced HepG2 cell model. This evidence concerns the gene STAT3 and metabolic dysfunction-associated steatotic liver disease.