These results indicate that primary resistance to gefitinib in the NSCLC cells with wild-type EGFR and KRAS mutation is associated with insensitive to gefitinib-induced EGFR downregulation, and gefitinib and curcumin combination-induced EGFR downregulation partially through proteasome-induced degradation of EGFR protein. Here, KRAS is linked to non-small cell lung carcinoma.