Objective: To investigate the clinical efficacy of endocrinotherapy in treatment of breast cancer patients with hormone receptor (HR)-negative primary lesion and HR-positive axillary lymph node metastases. Methods: Sixty-seven breast cancer patients with HR-negative primary lesion and HR-positive axillary lymph node metastases admitted from January 2011 to January 2016 were randomly designated to observation group (33 cases) and control group (34 cases). Patients in both groups received the same chemoradiotherapy regimen, while those in observation group were additionally given administration of tamoxifen (pre-menopausal patients) or letrozole (post-menopausal patients) after chemotherapy. The recurrence/metastasis and survival rates of the two groups of patients were compared. Results: All patients were followed up for 12 to 60 months, during which time, recurrence/metastasis occurred in 13 cases and death occurred in 7 cases in observation group, and recurrence/metastasis occurred in 19 cases and death occurred in 15 cases in control group. The incidence of recurrence/metastasis of the two groups showed no significant difference (P>0.05), while the rate of death due to recurrence/metastasis was significantly lower in observation group than that in control group (P<0.05). The 1-, 3- and 5-year disease-free survival (DFS) rate was 100%, 81.8% and 72.7% in observation group and was 100%, 58.8% and 47.1% in control group respectively; the 1-, 3- and 5-year overall survival (OS) rate was 100%, 90.9% and 81.8% in observation group and was 100%, 70.6% and 58.8% in control group. Both 3- and 5-year DFS and OS in observation group were significantly higher than those in control group (all P<0.05). Conclusion: Attention should be paid to the molecular classification of primary lesion and axillary lymph node metastasis in breast cancer patients. Postoperative endocrinotherapy may improve the survival and reduce the risk of death for breast cancer patients with HR-negative primary lesion and HR-positive axillary lymph node metastases.