Therefore, in hydroxytyrosol treated melanoma cells we report a dose-dependent induction of the intrinsic apoptotic pathway through the activation of pro-apoptotic proteins such as p53 and caspases-9 and -3, the down regulation of survival proteins such as PARP and AKT, the increased expression of γH2AX protein, as well as the inhibition of cell colony formation. This evidence concerns the gene TP53 and melanoma.