The upregulation of pro-apoptotic genes (P53, Bax, Caspase 3, and Caspase 9) and the downregulation of the anti-apoptotic genes (MMP1, CDK4, and Bcl2) after the treatment with chalcones 3e and 3f implicit the inhibition of cancer cells through the intrinsic pathway of apoptosis, which was a positive correlation between the cytotoxic efficacy of the compounds and apoptosis in A549 cells. This evidence concerns the gene CDK4 and cancer.