As manufactured nanoparticles, fullerene nanoparticles were used as the model to research the manufactured nanoparticles entering into cells and hence have been rapidly developed for biomedical uses. Human mesenchymal stem cells (hMSCs) have become the most widely used seeding cells in tissue engineering because they are readily obtained without ethical problems and are multipotent with regard to adipogenic, chondrogenic, and osteogenic lineages. Because of their favorable biological and cellular activities, C60 carboxyl derivatives are among the most widely studied C60 derivatives. FITC labeled C60(C(COOH)2)2 nanoparticles were charactered by FTIR, ESI-MS, XPS and DLS. The effects of C60(C(COOH)2)2-FITC on proliferation and differentiation of human mesenchymal stem cells (hMSCs) in vitro were observed. The fullerene nanoparticles are quickly internalized by the cells and they had low toxicity to proliferation of hMSCs. The C60(C(COOH)2)2 nanoparticles could promote cell proliferation, enhance osteoclast differentiation of hMSCs.