Here, through bioinformatics analysis, sample detection, transcriptome-wide high-resolution m6A-seq, RNA-seq and RIP-seq assay analyses, and cell biological analyses, we demonstrated that the m6A reader YTHDF1 regulates HPSCC iron uptake via m6A-modified TFRC mRNA, thereby regulating tumorigenesis and tumor proliferation. This evidence concerns the gene YTHDF1 and neoplasm.