Epidemiological studies have shown that high consumption of fruits and vegetables is associated with reduced risk of cancer. Phytochemicals, mainly phenolics and flavonoids, have been suggested to be responsible for these health benefits. However, the molecular mechanisms of the anticancer effects of fruits and vegetables are not fully understood. Fourteen grape varieties were analyzed for the profiles of total phenolics, total flavonoids, and trans-resveratrol. Phytochemicals in those grapes have potent antioxidant and antiproliferative activities. In addition, thirteen grape varieties and fourteen common phytochemicals were evaluated for their ability to induce mammalian phase II detoxification enzyme ? quinone reductase. Grape phytochemicals had strong activity in quinone reductase induction and potent antiproliferative activities toward Hepa1c1c7 cells. These results support the hypothesis that phytochemicals prevent cancer by acting as free radical scavengers and/or inducers of phase II detoxifying enzymes in the initiation stage, and/or as cell proliferation suppressors in the promotion/progression stages. Combinations of selected fruits and phytochemicals were studied for their antioxidant activity, antiproliferative activity, and induction of quinone reductase. The combination of apple extracts and quercetin 3-b-D-glucoside (Q3G) exhibited more potent antiproliferative activity when compared to the apple extracts and Q3G alone. The combination of grape extracts and quercetin, genistein, and resveratrol showed higher induction activity of quinone reductase than grape extracts and phytochemicals alone. In conclusion, we have demonstrated that the additive and synergistic effects of phytochemicals in fruits are responsible for their potent antioxidant activity, antiproliferative activity, and phase II detoxifying enzyme induction activity, and that the health benefit of a diet rich in fruits is attributed to the complex mixture of phytochemicals and their interactions present in those foods.