Objective：The present study aims to determine whether pharmacological activation of the transcriptional coactivator with PDZ-binding motif Tafazzin（TAZ） by chemical TM-25659 can promote osteogenic differentiation and bone formation of adipose-derived stem cells（ADSCs）in vitro and in vivo. Methods：Human ADSCs were isolated and expanded in vitro. The changing expressions of TAZ during ADSCs differentiation at different time points were measured by Western blot and real-time quantitative reverse transcription polymerase chain reaction（PCR）. Alizarin red S and oil red O staining were used to detect osteogenic and adipogenic effects. The ADSCs following initial osteogenic differentiation and TM-25659 were loaded on scaffold β-tricalcium phosphate（β-TCP）and then subcutaneously implanted into nude mice. Six weeks later，the results of bone formation in vivo after implantation of the ADSCs were measured and compared by Hematoxylin-Eosin staining，Masson staining and immunohistochemistry staining. Results：TAZ was upregulated during osteogenic differentiation of ADSCs but downregulated during adipogenic differentiation. Pharmacological activation of TAZ by TM-25659 promotes osteogenic differentiation of ADSCs in vitro. The transient treatment of ADSCs with TM-25659 significantly enhances new bone regeneration of ADSCs in vivo. Conclusion：TAZ is a key mediator for promoting osteogenic differentiation of ADSCs. The pharmacological activation of TAZ in ADSCs might become a feasible treatment for bone regeneration and repair.