Background: Endogenous estrogens play an important role in the development of breast cancer. Octylphenol (OP) and genistein (GEN) are estrogen-like chemicals. Prepubertal estradiol and genistein exposure can up-regulate BRCA1 mRNA in mammary gland and reduce futuer breast cancer risk. In the present study, the effects of prepubertal exposure to high-dose OP and GEN on mammary carcinogenesis and the association with the expression of BRCA1 and ERα were investigated. Methods: Prepubertal female Sprague–Dawley rats were exposed to 20, 40, 80mg/kg OP daily from postnatal day (PND) 22–28, subsequently, the rats were given a single dose of 100mg/kg 7,12-dimethylbenz [a] anthracene (DMBA) on PND42 to induce mammary tumor. Results: The incidence of DMBA-induced mammary tumors significantly decreased when rats were treated with 40mg/kg OP. BRCA1 mRNA and protein expression were found up-regulated and ERα expression was down-regulated in the mammary tumor when rats were exposed to 40mg/kg octylphenol. Conclusion: Exposure 40mg/kg octylphenol can reduce later breast cancer risk in prepubertal Sprague–Dawley rats, the protective effect of OP is associated with persistent up-regulation of BRCA1 and down-regulation of ERα in the mammary tumor.