Garlic extract in water, supplemented with copper, exerts an enhanced anti-proliferative and a caspase-independent apoptotic activity in a human hepatocarcinoma HepG2 cancer cell line. Furthermore, a DNA double strand break downstream, likely responsible for the observed cell death in HepG2 cell, was evidenced by an early over expression of p53 and p21. This observed synergistic antiproliferative and antitumor capability of water garlic extract, in the presence of copper, might be useful as new tool in cancer prevention and therapy.