Background: Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. A series of clinical studies have shown that anti-angiogenic drugs combined with chemotherapy enable to improve the efficacy of HER2-negative advanced/metastatic breast cancer(MBC). Methods: Patients with HER2-negative MBC with less than two lines of systemic therapy were enrolled in this open-label, controlled, phase II trial. Patients with measurable disease were randomly assigned, in a 1:1 ratio, to receive oral apatinib (250 mg once daily) combined with chemotherapy(A+CT) or chemotherapy(CT) alone (the physician’s choice) until disease progression or intolerable toxicity. The primary end point was progression-free survival(PFS), which was assessed by investigator and was analyzed on an intention-to-treat basis. Results: Between August 2017 and January 2021, of the 80 patients who underwent randomization, 40 were assigned to receive apatinib plus chemotherapy(A+CT) and 40 were assigned to receive standard therapy(CT). As of January 2022, 10 patient had not undergone response evaluation or dropout, 70 patients(36 patients in A+CT, 34 patients in CT were finally included with PFS events and 72 patients were included in safety set. Median PFS was significantly longer in A+CT than in CT (182 days vs 63 days; P = 0.043);The median PFS of TNBC subgroup (11 in A+CT group, 14 in CT) was longer in the aptinib group than in CT group (167 days vs 63 days; P = 0.637);The median PFS of HR+ subgroup(25 in apatinib group, 20 in chemotherapy group) was longer in the aptinib group than in CT group (259 days vs 56 days; P = 0.054);The median PFS of patients with liver metastases(19 in apatinib group, 17 in chemotherapy group) was longer in the aptinib group than in the CT group (151 days vs 54 days; P = 0.191); The severe adverse reactions (grade 3/4) were neutropenia(22.2% vs 13.9%), hypertension(11.1% vs 0.0%), leukopenia(8.3% vs 8,3%), hypokalemia(8.3% vs 2.8%), anemia(5.6% vs 11.1%), ALT(2.8% vs 8.3%), AST(0.0% vs 5.6%) in the apatinib group and the CT, respectively. Proteinuria did not occur in both groups. Treatment delay or dose reduction owing to adverse event was 16.7% and 11.1%, respectively. Treatment discontinuation owing to adverse event was 23.5% and 8.8%, respectively. Conclusions: Apatinib combined with chemotherapy showed a significant improvements in PFS and a manageable safety profile in HER2 negative MBC.