Oxidative stress may play a partial role in chemically induced tumorigenesis in mice. Herein, we investigated the preventive effect of vitamin E on 4-nitroquinoline 1-oxide (4NQO)-induced oxidative damage on pulmonary nuclei and lung tumorigenesis in mice. At 4 weeks after 4NQO injection, the levels of nuclear thiobarbituric acid substances (TBARS) and DNA single strand breaks (DNA-SSB) in the lungs of mice treated with 4NQO were significantly higher than those in the control mice. The 4NQO-induced oxidative stress on the nuclei and DNA-SSB were significantly inhibited by vitamin E treatment. The nuclear alpha-tocopherol level in the 4NQO-treated group was significantly lower than that in the control, but the plasma alpha-tocopherol level in the former was slightly lower than that in the latter. Vitamin E feeding compensated the decrease of the level in the nuclei and plasma. The feeding on excessive vitamin E for 23 weeks after 4NQO injection could partly reduce the lung tumor incidence as well as lung tumor multiplicity in mice. These findings suggest that vitamin E could partly suppress 4NQO-induced lung tumorigenesis in mice, probably through the inhibition of 4NQO-induced oxidative damage on the nuclei.