Although a large body of knowledge has established the mechanisms by which EGFR activates STAT3 through JAK or Src48, in this study, we show a novel mechanism by which activated EGFR enhances H3K23 acetylation and TRIM24 expression, promoting the association of TRIM24 with H3K23ac and STAT3, and facilitating STAT3 interaction with chromatin, leading to downstream signaling activation to drive glioma tumorigenesis. The gene discussed is EGFR; the disease is central nervous system cancer.