Here, we show that Notch inhibition, induced by short time exposure to chalcone–derived molecule 8 at low micro molar concentrations, results in anti-proliferative and pro-apoptotic effects in several human T-ALL cells, which were reverted by N1ICD overexpression, thus demonstrating that Notch1 inhibition is responsible, at least in part, of the growth inhibitory effect. Here, NOTCH1 is linked to acute lymphoblastic leukemia.