Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. However, the efficacy and safety data of eribulin for the ABC in Chinese patients is lacking, whether as first, second, or third-line regimens. This study aimed to evaluate the clinical effectiveness, safety, and treatment pattern of eribulin in first to third-line settings in Chinese ABC patients. Methods: Patients with histologically confirmed advanced breast cancer, who previously received ≤2 lines of treatment for metastatic disease were enrolled. In HR+/HER2- ABC, eribulin monotherapy was used; in HER2+ ABC, eribulin plus anti-HER2 targeted therapy were used; in metastasis triple-negative breast cancer (mTNBC), eribulin plus immunotherapy/chemotherapy were used. Primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: Forty-seven patients were enrolled from 2021.1.1 to 2021.10.20, including 41 metastatic and 6 de novo ABC patients. Eribulin was used as first-line therapy in 12 (25.5%) patients, second-line therapy in 24 patients (51.1%), and third-line therapy in 11 (23.1%) patients. More than 90% of the patients did not receive gemcitabine or vinorelbine, and 30.0% of them did not receive anthracycline or taxane previously. DCR was 70.2%, as 24 cases (51.1%) had stable disease and 9 cases (19.1%) had complete or partial remission. In subgroup analysis, median PFSs of 9.6 (95% CI: 6.5-12.7), 7.1 (95%CI: 4.4-9.8), and 5.6 (95%CI: 3.8-7.5) months were observed in patients receiving eribulin as first-, second-, and third-line therapy, respectively. In addition, median PFSs were 7.1 (95% CI: 5.1-9.3), 9.6 (95%CI: 3.6-15.7), 4.6 (95%CI: 4.6-4.6) and 5.8 (95%CI: 4.4-7.3) months for HR+/HER2-, HR+/HER2+, HR-/HER2+, and mTNBC patients, respectively. Other results from the subgroups analysis were shown in table. Common treatment-related toxicity was hematological toxicities including leukopenia (23%), neutropenia (17%), and thrombocytopenia (10%). There was no ≥grade 3 adverse events and no adverse event-related treatment discontinuation. Conclusions: Eribulin monotherapy or combined with targeted therapy was effective and well-tolerated as the first to third lines of treatment in ABC. This promising therapeutic outcome might warrant further studies in early eribulin administration in ABC patients. Clinical trial information: NCT04683445.