Intriguingly, we first detected a significant increase in the m6A methyltransferase METTL16 in mice and cell NAFLD models, and further confirmed that the expression levels of downstream target genes CIDEA were remarkably upregulated, which implied that METTL16 could become a novel molecular indicator and a potential therapeutic target for NAFLD. Here, METTL16 is linked to metabolic dysfunction-associated steatotic liver disease.