Background: Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors, accounting for < 1% of all adult malignancies. Although surgery combined with radiation results in high local control rates in localized STSs, high-risk patients (pts) have only 50% 5-year survival. Moreover, chemotherapy has been shown to be lack of consistent overall survival benefit in clinical trials. The vascular endothelial growth factor (VEGF) signaling mediated tumor growth plays an important role in the pathogenesis of several STSs subgroups. This study aimed to explore the efficacy and safety of apatinib, an oral tyrosine kinase inhibitor targeting VEFGR-2, in pts with advanced STS after failure of prior chemotherapy preliminarily. Methods: This is a prospective, open-label, single-arm, multi-center phase II study, with planned sample size of 53. All pts with histologically confirmed STSs experienced failure of prior chemotherapy in the last 6 months. Oral apatinib (500 mg) was given to pts daily in cycles of 28 days until disease progression, death or unacceptable toxicity. The primary outcome was 6-month progression-free survival (PFS) rate. Results: 35 pts were enrolled as of January 16, 2018. The top 3 subtypes of STSs were alveolar soft tissue sarcoma (20%), leiomyosarcoma (17%) and liposarcoma (12%). The 6-month PFS rate was not reached. Of 35 pts, 23 were available for response evaluation: 6 achieved partial response, 15 had stable disease, and 2 had progressive disease, resulting in an overall response rate of 26.1% and a disease control rate of 91.3%, at primary response. 33 pts were eligible for safety evaluation. The incidence of adverse events (AEs) was 93.9%. The most common AEs were hypertension (63.6%), proteinuria (60.6%), and hand-foot syndrome (54.6%). The incidence of Grade 3-4 AEs was 42.2%, and hypertension (30.0%) was the most common Grade 3-4 AEs. Conclusions: Current results demonstrated encouraging signs of anti-tumor activity, and well-tolerated toxicity of apatinib in previously treated advanced STSs. Clinical trial information: NCT03064243