Since Sp1 has been found to regulated EGFR transcription through interacting with HDAC1 in cancer cells [37], we revealed for the first time that combination of gefitinib and curcumin decreased EGFR mRNA level and luciferase activity through suppressing Sp1 and blocking interaction of Sp1 and HDAC1 in the gefitinib-resistant NSCLC cells, and this was accompanied by decreased expression of other Sp1-dependent proteins survivin, VEGF and c-Met, and enhanced induction of autophagy and apoptosis. The gene discussed is EGFR; the disease is cancer.