Synovial sarcoma is a rare malignant tumor. The role of apatinib in synovial sarcoma remains unclear. In this study, we aimed to determine the biological functions and the potential molecular mechanism of action of apatinib in synovial sarcoma.SW982 cells were stimulated with apatinib. The relative expression of the genes was determined by performing qPCR. Protein levels were evaluated by western blot and immunohistochemistry assays. Proliferation, apoptosis, migration, and invasion of SW982 cells were determined by the CCK-8 assay, clone formation assay, flow cytometry, wound healing, and the transwell assay, respectively. Additionally, SW982 cells were injected into mice to induce synovial sarcoma.Apatinib decreased the proliferation, migration, and invasion but increased the apoptosis of SW982 cells. Apatinib repressed tumor growth in vivo and elevated miR-34a-5p in SW982 cells. The inhibition of miR-34a-5p repressed the reduction of proliferation, migration, and invasion and also the elevation of apoptosis in apatinib-treated SW982 cells. The luciferase activity decreased after cotransfection of the miR-34a-5p mimic and the wild-type HOXA13 vector. Additionally, an increase in miR-34a-5p repressed the levels of HOXA13 mRNA and protein. Moreover, HOXA13 reversed these patterns caused by the inhibition of miR-34a-5p in apatinib-treated SW982 cells.Apatinib elevated miR-34a-5p and reduced HOXA13, leading to a significant decrease in proliferation, migration, and invasion, along with an enhancement of apoptosis in SW982 cells. Apatinib suppressed tumorigenesis and tumor growth in SW982 cells in vivo.Copyright © 2022 Qi Feng et al.