Abstract: Giant cell tumor of bone is a type of aggressive tumor characterized by osteolytic bone destruction. After surgery, the recurrence rate is high. Malignant transformation and metastasis occur in few cases. In recent years, it has been reported that RANKL is over-expressed in giant cell tumor of bone, and monoclonal antibodies against RANKL (denosumab) have demonstrated great success in the treatment of high-grade, unresectable, and metastatic giant cell tumors of the bone. It can debase the surgical staging, increase the probability of surgical resection, decrease function loss after surgery, and inhibit tumor progression with rare adverse reactions. Meanwhile, the characteristic changes in the images and pathology after the use of denosumab raise new questions for clinical diagnosis and surgical treatment. Finally, denosumab is still partially controversial in terms of drug use time and safety; it remains to be further confirmed by clinical trials.