Tamoxifen(TAM) is one of the most effective endocrine treatment for estrogen receptor(ER)-positive breast cancer, however drug resistance greatly prevents patients to get benefit from it.The purpose of this study is to uncover the role of Beclin 1 in tamoxifen resistance and in prognosis of ER positive breast cancer.We established a tamoxifen resistant ER-positive breast cancer cell subline MCF-7R with higher Beclin 1 and human epidermal growth factor receptor 2(HER2) levels than MCF-7.Silencing Beclin 1 significantly promoted TAM sensitivity and decreased levels of HER2 and HER2 downstream effectors of MCF-7 and MCF-7R in vitro.Overexpression of HER2 could reverse formerly increased TAM sensitivity in Beclin 1 downregulated cell.Beclin 1 level was not only positively correlated with level of HER2 but also negatively correlated with overall survival of ER-positive breast cancer patients.Using bioinformatic methods, Beclin 1 mRNA was found to be negatively correlated with overall survival in breast cancer patients receiving TAM treatment.This study indicated for the first time a regulatory role of Beclin 1 in down-regulation of HER2 expression, which could be an underlying mechanism contribute to enhanced tamoxifen sensitivity and favorable outcome in Beclin l-low and ER-positive breast cancer.