The development of methods of cancer prevention is a particularly important issue. We have proposed a strategy termed "combination-oriented molecular-targeting prevention" of cancer. As the molecular target of our model, we focused on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor. TRAIL is a cytokine from immune cells and is important for immune surveillance and defense mechanisms against cancer cells. First, we searched for food factors inducing the expression of death receptor 5 (DR5), one of the TRAIL receptors. DR5 is specifically expressed on the membrane of cancer cells, not on that of normal cells. We found that many food factors markedly induced DR5 expression, enhancing TRAIL sensitivity against cancer cells. We next found that lactic acid bacteria induced endogenous TRAIL production in human peripheral blood mononuclear cells (PBMCs). Importantly, lactic acid bacteria increased the NK activity of PBMCs against cancer cells. Moreover, we found that butyric acid bacterium, one of the antiflatulents, induced the release of endogenous TRAIL from polymorphonuclear neutrophils. The butyric acid bacterium was proven effective against cancer cells by inducing apoptosis in vivo as well as in vitro. Taken together, these results strongly suggest that the strategy of "combination of DR5-inducing food factors and TRAIL-inducing food factors" as molecular-targeting prevention of cancer will be a practical approach.