Abstract: Objective To explore the effectiveness and safety of everolimus (EVE) combined with other endocrine drugs on endocrine-resistant hormone receptor-positive (HR-positive) metastatic breast cancer patients. Methods The curative effect and adverse reactions of 24 endocrine-resistant HR-positive advanced breast cancer patients who received everolimus combined with tamoxifen (TAM), aromatase inhibitors (AIs) or fulvestrant (Ful) in Chinese PLA General Hospital from February 1, 2012 to June 1, 2015 were retrospectively analyzed. Results After 10 months of follow-up, the median time to treatment failure (mTTF) was 4(95%CI, 2.2 to 5.8) months, and the median overall survival (mOS) was 15.8 months (95%CI, 9.0 to 22.7). The objective response rate (ORR) was 20.9%, and the disease control rate (DCR) was 62.5%. EVE combined with TAM, AIs, and Ful had a median TTF of 2 months, 4 months, and 5.5 months, respectively (P=0.731), and the median OS was 9.6 months, 15.8 months, 11.4 months respectively (P=0.829). Univariate analysis showed that estrogen receptor (ER)/progesterone receptor (PR) status and AIs resistance were the factors affecting TTF and PR, and histological grade was the factor that affecting the OS. The occurrence of stomatitis was significantly correlated with TTF and OS. There was no correlation between EVE's curative effect, patients' prognosis and the number of previously rescued treatment lines. Cox regression analysis showed that AIs resistance (HR, 0.082; 95%CI, 0.019 to 0.353) and stomatitis (HR, 0.148; 95%CI, 0.050 to 0.435) were independent prognostic factors of TTF. The most common adverse reactions were stomatitis (83.33%), fatigue (37.50%), non-infectious lung disease (25.00%), infection (33.33%), skin rash (16.70%)and hyperglycemia (12.50%), nausea and vomiting (39.17%), diarrhea (25.00%), cough (50.00%). The most common Ⅲ /Ⅳ adverse events were non-infectious lung disease (16.67%), stomatitis (4.17%) and infection (4.17%). Conclusion Everolimus combined with other endocrine drugs is definitely effective on endocrine-resistant HR-positive advanced breast cancer. Everolimus can prolong the progression of endocrine-resistant diseases, and it is well tolerated.