In summary, we identify the PBX2‐PRMT1‐SWI/SNF‐IGF2BP2 axis as a key driver of tumor growth and CBP resistance in HNSCC, revealing non‐methyltransferase functions of PRMT1 and its potential as a therapeutic target to enhance CBP efficacy. The gene discussed is IGF2BP2; the disease is head and neck squamous cell carcinoma.