Here, we have provided the first evidence that curcumin and gefitinib synergistically inhibit the growth of gefitinib-resistant NSCLC cells by downregulating Sp1/EGFR activity and the receptor tyrosine kinase pathways, thereby inducing autophagic cell death and autophagy-mediated apoptosis. The gene discussed is SP1; the disease is non-small cell lung carcinoma.