N-Methyladenosine (mA) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N nitrogen of adenosine. However, the roles of mA in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3' UTR (near to stop codon) of the c-Myc transcript to install the mA modification, thereby enhancing its stability. Furthermore, results revealed that YTH N-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the mA-increased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated mA modification, thereby giving rise to OSCC tumorigenesis.