SH2 domain‐containing adapter protein F (SHF) is identified as tumor suppressor in glioblastoma and its negative regulation of STAT3 activity is characterized by disrupting acetylated STAT3 dimerization and STAT3‐DNMT1 interaction, thereby relieving methylation of tumor suppressor genes, and a peptide targeting STAT3‐binding sites of SHF is demonstrated as a suppressive strategy. This evidence concerns the gene SHF and glioblastoma.