In the present study, in order to find new potential anti-cancer agents against EGFR-TK, a series of 47 previous synthesized chalcone derivatives [39] were screened in vitro for cytotoxicity towards two cancer cell lines with wild type EGFR expression derived from a human epidermoid carcinoma (A431) and human lung adenocarcinoma (A549), and two human lung cancer cell lines with EGFR mutants (H1975 and H1650) using the surrogate 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Here, EGFR is linked to squamous cell carcinoma.