Abstract Objective The expression of HERG in common bone tumors is scarcely reported and there is a lack of dedicated studies. This study aimed to investigated the expression of HERG in several common musculoskeletal tumors. Methods Immunohistochemical staining, RT-PCR, and Western blotting were used to observe HERG expression differences in various tissues and cell lines. Results HERG was differentially expressed in different malignant tumors, both at a differential protein level and localization within tumors. HERG was not expressed in normal bone tissue. The HERG inhibitor E-4031 markedly inhibited the proliferation of osteosarcoma cell lines. Conclusion HERG was highly expressed in malignant tumors. Blocking of HERG can effectively inhibit the proliferation of bone tumors.