Background: Anthracycline and ifosfomide-based chemotherapy is the main neoadjuvant treatment option for resectable high-risk STS with severe myelosuppression and other side effects. Anlotinib has been approved as second-line treatment for most of advanced STS by the Chinese agency. This study was conducted to evaluate the efficacy and safety of anlotinib in combination with doxorubicin in the neoadjuvant treatment of patients with resectable high-risk STS to reduce the toxicity of chemotherapy. Methods: This is a single-center, prospective study. Eligible patients were those ≥18years old, ECOG performance state of 0-1, with histologically confirmed locally resectable high-risk STS. All patients received a preoperative combination of anlotinib (12mg once daily, on for 2 weeks, off for 1 week) and doxorubicin (75mg /m2, IV, D1-2, every 3 weeks) .The combination treatment was repeated 2 to 3 cycles before operation. The primary endpoint was objective response rate (ORR), and the second endpoints were Disease control rate (DCR), and side effects. Results: Between December 2020 and December 2022, 13 patients were evaluated, including 4 synovial sarcoma, 3 undifferentiated sarcoma, 3 spindle cell sarcoma, 2 liposarcoma, 1 angiosarcoma. The median age was 35 years. 1 patients (7.69%) achieved a confirmed partial response (PR) and 7 (53.85%) had stable disease (SD). The ORR and DCR were 7.69% and 61.54% respectively. All patients underwent marginal or extensive excision of the tumor and none underwent amputation. Most of Treatment-related adverse events included neutropenia 5 (38.46%), hypothyroidism 3 (23.08%), anemia 2(15.38%). Three patients experienced grade 3 or 4 adverse events, neutropenia (1/13, 7.69%) and tumor hemorrhage (2/13, 15.38%). No wound complications such as infection, delayed healing or haematoma occurred. Conclusions: This study suggested that the combination of anlotinib and doxorubicin might be a option for neoadjuvant therapy for patients with resectable high-risk STS due to the anti-tumor activity and acceptable toxicity.