OBJECTIVE: To investigate the correlation of blood concentrations of tamoxifen (TAM) and its metabolites with endometrial hyperplasia in estrogen receptor (ER)-positive breast cancer patients. METHODS: A total of 69 patients with ER-positive breast cancer selected from our hospital during Mar. 2015-Apr. 2016 received TAM (twice a day, one tablet each time) for more than 6 months. According to endometrial thickness, they were divided into abnormal hyperplasia group (40 cases) and normal group (29 cases). The steady state concentrations of TAM and its metabolites [4-OH-tamoxifen (OHT), N-demethylation tamoxifen (DMT), Endoxifen] were determined by HPLC-FLU. The correlation of blood concentration and other factors with endometrial thickness were investigated by Pearson test and multiple regression analysis. RESULTS: The medication time and Endoxifen steady state concentration in abnormal hyperplasia group were both significantly longer or higher than normal group, with statistical significance (P<0.05). There was no statistical significance in age, BMI, complication and steady state concentrations of TAM, OHT and DMT between 2 groups (P>0.05). The endometrial thickness was positively correlated with Endoxifen steady state concentration and medication time (r=0.447, 0.460,P<0.05). Using endometrial thickness (y) as dependent variable, medication time (x1) and Endoxifen steady state concentration (x2) as independent variable, multiple regression analysis was conducted. Multiple regression equation was calculated as follows: y=2.436+0.123x1+0.082x2(F=12.610,r=0.526,P<0.05). CONCLUSIONS: Medication time and Endoxifen steady state concentration may be related to endometrial hyperplasia, which can provide reference for predicting TAM induced endometrial abnormal hyperplasia in ER-positive breast cancer patients.