Methyltransferase-like 3 (METTL3) catalyses N6-methyladenosine (m 6 A) modification on messenger RNA (mRNA) and participates in a wide range of biological functions via epigenetically regulating gene expression. Recent studies suggested that dysregulation of METTL3 is associated with multiple human cancers; however, the role of METTL3 in lung cancer remains unclear. In the present study, through transcriptome analysis of lung cancer patients, we found that METTL3 is overexpressed in lung cancer patients and is associated with poor patient survival. More importantly, combining both in vitro and in vivo models, we revealed that in lung cancer cells, METTL3 overexpression activates PI3K/AKT/mTOR pathway and mTORmediated protein synthesis. Mechanistically, METTL3 promotes PI3K expression by introducing m 6 A modification in PI3K 3 0 untranslated region (3 0 UTR). Elevated PI3K level then activates downstream AKT and mTOR signalling pathway and results in rapid cancer cell proliferation and metastasis. Taken together, our study reveals that METTL3-mediated m 6 A methylation promotes lung cancer progression via activating PI3K/AKT/mTOR pathway.