Estrogen may contribute to the development of smoking-induced lung cancer in women. To test this hypothesis, an mouse model was used to investigate the effects of 17 beta-estradiol (E2) on benzo[a]pyrene (B[a]P)-induced lung carcinogenesis. We found that B[a]P could cause oxidative stress damage, upregulate mitochondrial cytochrome-c and caspase-3 expression, induce lung carcinogenesis in female mice, E2 promoted these effects of B[a]P while tamoxifen (TAM) inhibited this effects of E2. We conclude that E2 can promote the tumorigenic effects of B[a]P in female mice, and oxidative stress damage and activation of cytochrome-c-mediated caspase-3 pathway may be involved in this process.