Given the encouraging results of TOPK targeting in other cancers and the limitations of current osteosarcoma regimens, we investigated the following: (a) expression of TOPK in public databases, with additional validation of this expression in human osteosarcoma tissues and cell lines; (b) correlation between TOPK expression and clinicopathology and outcomes of osteosarcoma patients; (c) functions of TOPK in osteosarcoma cell growth and proliferation; and (d) effects of a specific TOPK inhibitor on osteosarcoma cell proliferation, migration, and chemosensitivity. This evidence concerns the gene PBK and osteosarcoma.