Extracellular matrix (ECM) proteins serve a major role in the pathogenesis of aortic dissection (AD). The aim of the present study was to investigate the effect of osteoglycin (OGN), an ECM proteoglycan, on aortic dissection (AD), as well as the underlying mechanism. Thoracic aortic tissues from 20 patients with AD and healthy thoracic aortic tissue from 5 patients undergoing coronary artery bypass grafting were collected to detect OGN expression levels. Following OGN knockdown in rat aortic smooth muscle cells, cell proliferation was detected by performing Cell Counting Kit‑8 and BrdU assays, cell migration was assessed by performing the wound healing assay, cell invasion was detected by performing the Transwell assay, and VEGFR/AKT signaling pathway‑related protein expression levels were measured via western blotting. The results demonstrated that OGN expression was significantly downregulated in patients with AD compared with healthy controls. Compared with the si‑negative control (NC) group, OGN knockdown promoted RASMC proliferation and migration. Compared with the si‑NC group, OGN knockdown also significantly enhanced the phosphorylation of the downstream signaling molecules of VEGFR, including AKT and ERK1/2, in VEGF‑stimulated RASMCs. Collectively, the present study indicated that OGN knockdown facilitated RASMC proliferation and migration by activating AKT and ERK1/2 signaling. Therefore, OGN may serve as a novel therapeutic target for AD.