In this study, we demonstrated that the EGF-mediated Ca2+ response in NSCLC cells was altered depending on gefitinib resistance and [Ca2+]e restriction on gefitinib-sensitive and gefitinib-resistant cells elicited identical [Ca2+]i oscillations, which were associated with the modulation of gefitinib efficacy. Here, EGF is linked to non-small cell lung carcinoma.