Compared to viral carriers, non-viral gene delivery systems showed good biocompatibility and safety, but low transfection efficiencies. Fortunately, the mechanism of folic acid uptake by cells to promote targeting and internalization could improve transfection rates. In this study, folate-chitosan and one kind of cholesterol derivatives CHETA (Cholest-5-en-3beta-yl[2-[[4-[(carboxymethyl)dithio]-1-iminobutyl]amino]ethyl] carbamate, C(36)H(61)N(3)O(4)S(2)) were synthesized to prepare the charge changing Solid Lipid Nanoparticles (Folate-chitosan-CHETA-Sln) by a reverse micelle-double emulsion method. The resulted particles showed the distributions of size and zeta potential were 254.5 +/- 20 nm and -40.5 +/- 0.8 mV, respectively. The image observed by scanning electron microscopy (SEM) showed that Folate-chitosan-CHETA-Sln was spherical in shape. Moreover, after reaction with a disulfide reducing agent dithiothreitol (DTT), the zeta potential changed from negative to positive (20.5 +/- 1.9 mV). The results of transfection showed that Folate-chitosan-CHETA-Sln enhanced the reporter gene expression against a folate receptor over-expressing cell line (SKOV3 cells) compared to a folate receptor deficient cell line (A549 cells) and did not induce obvious cytotoxicity against HEK 293 cells. In addition, the presence of serum did not affect the transfectivity of Folate-chitosan-CHETA-Sln complexes. In conclusion, Folate-chitosan-CHETA-Slns with proper physical characteristics and high transfection efficiency might act as a novel non-viral gene delivery system.