IL-11Rα is an important cytokine receptor that links oxidative stress and compensatory proliferation. Mounting evidence has demonstrated that IL-11Rα regulates autoimmune demyelination and the invasion and proliferation of cancer cells, making it an important therapeutic target for molecular targeted therapy. Moreover, overexpression of IL-11Rα indicates a poor long-term prognosis in cancer patients. However, the expression status and its potential as a biomarker for diagnosis, tumor imaging, and prognosis in osteosarcoma remain to be determined. We report here that IL-11Rα is highly expressed in osteosarcoma and near-infrared (NIR)-labeled IL-11Rα imaging agent could detect osteosarcoma in mouse tumor xenografts. In a panel of human osteosarcoma specimens, IL-11Rα protein was positively stained in most cases by immunohistochemistry. Western blot analysis and flow cytometry showed that IL-11Rα was overexpressed in osteosarcoma SOSP-9607 cells. Cell-binding assay demonstrated specific binding of the IL-11Rα targeted imaging agent to osteosarcoma SOSP-9607 cells in vitro. In addition, administration of an IL-11Rα targeted imaging agent in a nude mice orthotopic model resulted in selective accumulation of NIR fluorescent signals in the bone tumor as well as several metabolic organs. These results indicate that IL-11Rα is a potential target for the development of molecular targeted therapy and noninvasive tumor imaging in human osteosarcoma. Furthermore, NIR-labeled IL-11Rα imaging agent is a promising lead for the development of a tumor in vivo imaging method at the molecular level in the management of human osteosarcoma.