In this study, we used a group of cancer cell lines with either overexpressed or tyrosine kinase domain-mutated (ΔE746-A750 or L858R) EGFR to assess their responsiveness to cetuximab and gefitinib treatment and to evaluate HIF-1α as novel molecular marker for the therapeutic responses of the cancer cells to EGFR-targeted therapy. The gene discussed is EGFR; the disease is cancer.