This study was designed to determine the safety and clinical efficacy of metronomic chemotherapy combined with aromatase inhibitors (AIs) for hormone receptor (HR)-positive advanced breast cancer (ABC) patients who cannot tolerate conventional-dose chemotherapy. Postmenopausal patients with HR-positive ABC, who exhibited disease progression after first-line AIs treatment and who could not tolerate or rejected conventional chemotherapy, were enrolled in this study. Patients received capecitabine 500 mg PO TID (could be reduced to 500 mg QD in case of adverse effects) and exemestane 25 mg QD (after PD with letrozole) or letrozole 2.5 mg QD (after PD with exemestane). The primary endpoints were safety and tolerance, the secondary endpoints were objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and time to treatment failure (TTF). In our analysis of 44 patients, the median age was 64 years (range 38-90) and 68.2% patients had at least two recurrences or metastatic lesions. Grade 3 toxicities (hand-foot syndrome) were observed only in 4 of the patients. Most patients exhibited no or mild toxicities. After a median follow-up of 14.8 months, ORR was 70.5%, CBR-77.3%, PFS-16.2 months, and TTF-14.4 months. Metronomic oral capecitabine combined with AIs showed good efficacy, minimal toxicities, and good tolerance in HR-positive patients with ABC. It is a potential treatment option especially for postmenopausal HR-positive ABC patients in poor general condition who cannot tolerate conventional chemotherapy. Clinicaltrials.gov NCT01924078.