Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosisinduction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presentedthe possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosageand time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations(0 μM, 0.01 μM, 0.1 μM, 1 μM, 5 μM, 30 μM) and assessed apoptotic and osteogenic differentiation markerswith immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOLenhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1μM in GCTSC.Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL maybe considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulatingosteogenic differentiation of remaining tumor stromal cells after surgery.