Our study is the first to show that miR-21a-5p, miR-122-5p, miR-34a-5p and miR-103-3p expression and numerous of their target genes like, Srebf1, Tgfb1, Fasn and Cpt1a are modified by pirfenidone treatment in a MAFLD/NASH model as part of an improvement in molecular, histopathological and biochemical parameters. This evidence concerns the gene CPT1A and metabolic dysfunction-associated steatohepatitis.