Lung metastasis is the primary cause of death in osteosarcoma (OS) patients. A better understanding of the molecular mechanisms underlying OS tumorigenesis and metastasis is urgently needed to identify therapeutic targets. Microtubule actin crosslinking factor 1 (MACF1), which belongs to the spectraplakin family of cytoskeletal crosslinking proteins, is critical for cell migration and polarization due to its regulation of the cytoskeleton. Recently, MACF1 was indicated to be involved in the metastatic invasion of some human cancers, but the function of MACF1 in OS is still unclear.