In this study, we identified that YTHDF1 was significantly overexpressed and associated with a poor prognosis in HCC by bioinformatics analysis and tissue microarrays, and further revealed that YTHDF1 activated the PI3K/AKT/mTOR signaling pathway and induced EMT, leading to the enhanced proliferation, migration and invasion of HCC cells. Here, PIK3CA is linked to hepatocellular carcinoma.