Abstract: ObjectiveTo study the effect of folic acid coupling rate on anti-tumor property of folic acid-chitosan nanoparticles. MethodsFolate-chitosan complexes at different folic acid coupling rate were synthesized by using a reductive amidation reaction. The green fluorescent protein expression gene was encapsulated with complexes. The shape and size of nanoparticles were detected by electron microscope. The transfection efficiency and cell apoptosis rate were evaluated through the flow cytometer. ResultsThe nanoparticles presented the different sizes of （289.6±0.7）nm,（78.1±0.3）nm,（186.6±0.6）nm and （212.2±0.5）nm at different coupling ratio with 3%、 7.5%、11.2% and 17% with smooth and round shape. The transfection efficiency of nanoprticles at 7.5% coupling ratio was higher than unmodified nanoparticles (P＜0.01). Compared with the unmodified nanoparticles, the apoptosis rate of cells treaded by nanoprticles at 7.5% coupling ratio was higher and difference has statistical significance (P<0.01). ConclusionAfter modified by folic acid, the drug intake and apoptosis rate of HeLa cells are both enhanced. The folic acid coupling rate can influence the nanoparticles size, transfection efficiency and cell apoptosis.