Here, we found that silencing METTL3 sensitized arecoline-transformed OSCC to cisplatin treatment in vitro, and the combination of METTL3 knockdown and cisplatin yielded the most profound tumor inhibition effect on arecoline-transformed OSCC in vivo, suggesting that targeting METTL3 might be a wise strategy to improve therapeutic effects of cisplatin on OSCC patients, particularly in those who have a propensity of chewing areca nuts. Here, METTL3 is linked to neoplasm.