Overall, we described a HOXD‐AS2/STAT3 positive feedback loop in GBM that STAT3‐induced lncRNA HOXD‐AS2 interacted with protein IGF2BP2 to form a complex, upregulating IGF2 and STAT3 signaling and promoting the BCL2 anti‐apoptotic genes' expression, thus attenuating temozolomide sensitivity. The gene discussed is IGF2; the disease is glioblastoma.