In this study, novel liver targeted doxorubicin (DOX) loaded alginate (ALG) nanoparticles were prepared by CaCl2 crosslinking method. Glycyrrhetinic acid (GA, a liver targeted molecule) modified alginate (GA-ALG) was synthesized in a heterogeneous system, and the structure of GA-ALG and the substitu-tion degree of GA were analyzed by 1H NMR, FT-IR and elemental analysis. The drug release profile under the simulated physiological condition and cytotoxicity experiments of drug-loaded GA-ALG nanoparticles were carried out in vitro. Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that drug-loaded GA-ALG nanoparticles have spherical shape structure with the mean hydrodynamic diameter around 214 ± 11 nm. The drug release was shown to last 20 days, and the MTT assay suggested that drug-loaded GA-ALG nanoparticles had a distinct kill-ing effect on 7703 hepatocellular carcinoma cells. In this study, novel liver targeted doxorubicin (DOX) loaded alginate (ALG) nanoparticles were prepared by CaCl2 crosslinking method. Glycyrrhetinic acid (GA, a liver targeted molecule) modified alginate structure of GA-ALG and the substitutio degree of GA were analyzed by 1H NMR, FT-IR and elemental analysis. The drug release profile under the simulated physiological condition and cytotoxicity experiments of drug-loaded GA-ALG nanoparticles were carried out in In vitro. Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that drug-loaded GA-ALG nanoparticles have a spherical shape structure with the mean hydrodynamic diameter around 214 ± 11 nm. The drug release was shown for the last 20 days, and the MTT assay suggested that drug-loaded GA-ALG nanoparticles had a distinct kill-ing effect on 7703 hepatocellular carcinoma cells.