Here, we report that CBX4 promotes metastasis in osteosarcoma via transcriptionally upregulating Runx2, and that down-regulation of CBX4 by both casein kinase 1α (CK1α) and the carboxyl terminus of HSC70-interacting protein (CHIP) may provide strategies to target osteosarcoma patients with metastasis. Here, CBX4 is linked to osteosarcoma.