To observe the expression of ER alpha and SMRT in ER alpha-positive and -negative cell lines before and after treatment with tamoxifen (TAM).Breast cancer T47D cells (ER alpha-positive) and MDA-MB-231 cells (ER alpha-negative) were treated with TAM, cell viability was measured by MMT assay before and after TAM treatment. Flow cytometry (FCM) was applied to analyze apoptosis rate and cell cycle. Immunohistochemistry and Western blot were used to test ER alpha and SMRT expression in T-47D and MDA-MB-231 cells with and without TAM treatment.Proliferation rate of T-47D and MDA-MB-231 decreased after 0.10 mmol/L TAM treatment for 48 h compared with control group (P <0.05), especially that of T47D cells. The result of FCM showed that sub-diploid apoptosis peak was found in both cell lines after TAM treatment. Immunohistochemistry and Western blot indicated that T-47D cells presented ER alpha++ and SMRT++, and ER alpha expression decreased after TAM treatment, meanwhile, that of SMRT increased. MDA-MB-231 cells presented ER alpha-, SMRT-, and both expression levels increased slightly after TAM treatment.TAM can inhibit the proliferation of breast cancer cells by inducing cell apoptosis,which is associated with alteration of ER alpha and SMRT expression.