Water-soluble onion-like fullerene (OLF) derivatives were prepared by chemical bonding of L-cysteine, an important amino acid in organisms, to OLFs. The L-cysteine OLFs were characterized by SEM, XRD, IR, TGA and XPS. Results showed that hydrophilic groups added to the surface of OLFs such as -OH and -NH3 made L-cysteine OLFs good water-soluble derivatives. Experiments in mice demonstrated that the water-soluble fullerene derivatives were well distributed in the histolytic organism because of their excellent solubility and fluidity in humoral liquid.