AIM: To design,synthesize and to characterize N -methylene phosphonic chitosan derivatives for potential gene delivery carriers for hepatocyte-targeting. METHOD:Firstly,a water-soluble N -phosphonomethylated chitosan (MPCS) was prepared by reaction of chitosan with phosphorous acid and formaldehyde. To give galactosylated N -methylene phosphonic chitosan (Gal-MPCS),lactobionic acid was added and galactose group was introduced into the amino groups of MPCS. Lactosaminated N -methylene phosphonic chitosan (Lac-MPCS) was prepared by reaction of MPCS and α-lactose,followed by reaction with KBH_ 4 . RESULT and CONCLUSION: The degree of substitution of phosphonomethylation,galactosylation and lactosamination was stipulated to be 1.20,0.23 and 0.21 respectively. The chemical structure of the modified chitosan was characterized by FTIR, 1 HNMR, 13 CNMR and elemental analysis. Some physical behaviors were analyzed by X-ray diffraction and differential scanning calorimetry (DSC). The N -methylene phosphonic chitosan derivatives may be used as potential gene delivery carriers for hepatocyte-targeting.