GBM, characterized by a large number of M2‐like tumor‐associated macrophages (TAMs) and inflammatory factors in TME,[49, 50] lacks effective therapies, which leads to eventual tumor recurrence and poor survival.[51, 53] Despite the abundance of preclinical trials conducted to identify novel, effective therapies for GBM, translation into actual clinical benefit has been rare.[54] In this study, we demonstrated the crucial role of CYP2E1 in GBM by modulating M/Mφ reprogramming and a newly developed CYP2E1 inhibitor, Q11, significantly suppressed the growth of GBM. Here, CYP2E1 is linked to glioblastoma.