In summary, miR-379-5p can inhibit the expression of STAT1 through both transcriptional and translational levels, and then down-regulate the STAT1/HMGCS1 axis to improve FC overload, which suggested that miR-379-5p might be a novel regulator in cholesterol metabolism and improve liver damage in NAFLD. This evidence concerns the gene STAT1 and metabolic dysfunction-associated steatotic liver disease.