Fulvestrant 500mg has proved its clinical effectiveness in previous trials as primary or second line treatment of hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2-) post-menopausal advanced breast cancer. This real-world study aimed to investigate the efficacy and safety of Fulvestrant in HR+/HER2- Chinese advanced breast cancer patients. HR+/HER2- advanced breast cancer patients who received Fulvestrant 500mg from January 2015 to December 2018 in Beijing Cancer Hospital were enrolled in this retrospective study. Progression free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and adverse events (AEs) of Fulvestrant were investigated. In total 303 enrolled patients [median age was 51 years (range: 21-82)], 255 (84.2%) patients were at postmenopausal status at the start of Fulvestrant treatment and 264 patients (87.1%) had advanced breast cancer. The median PFS (95% confidence interval) was 14.1 months (10.1-18.0) for the first-line, 11.2 months (2.2-20.3) for the second-line and 6.7 months (4.8-8.5) for ≥third-line of Fulvestrant. The ORR and CBR were 3.8% and 86.8% for the first-line, 5.5% and 75.4% for the second-line, 1.1% and 61.1% for ≥third-line of Fulvestrant. The multivariate subgroup analyses showed, PFS was significantly longer for the patients with light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free interval. For patients receiving Fulvestrant after palliative chemotherapy, the median PFS was numerically greater in maintenance treatment group than those who progressed after chemotherapy. Only 5.0% of patients (15/303) experienced adverse events and majority were grade 1-2. The most common adverse event was headache and palpitation, with merely one patient had severe adverse event (pulmonary embolism). Fulvestrant is an effective, safe and well-tolerated treatment regimen in endocrine therapy for HR+/HER2- metastatic breast cancer. Light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free survival (DFS) might be the ideal condition of Fulvestrant treatment. Fulvestrant can be effective for premenopausal patients with drug-induced menopause. Patients of different luminal subtypes can benefit from Fulvestrant. For patients with visceral metastases, presence of liver metastases rather than lung metastases was poor prognostic factor. Fulvestrant may also be considered as a maintenance treatment after first-line palliative chemotherapy.© The author(s).