In this study, we successfully synthesized a novel glycyrrhetinic acid (GA) derivate compound as a liposomal carrier. Glycyrrhetinic acid-diaminododecane-cholesterol (GA-DA-CH) was synthesized from GA, diaminododecane, and cholesteryl hemisuccinate by two-step amidation under catalytic conditions. The chemical structures of GA-DA (glycyrrhetinic aciddiaminododecane) and GA-DA-CH were confirmed by Mass Spectrum (MS), Nuclear Magnetic Resonance (NMR) spectrometer, and analyzed by Fourier Transform Infrared spectroscopy modified liposomes (GA-DA-CH-Lips) were prepared, consisting of egg phosphatidylcholine, cholesterol , GA-DA-CH. GA-DA-CH was integrated into the liposomal capsule to promote hepatocellular carcinoma targeting. The particle size of GA-DA-CH-Lips was calculated to be between 122.87 and 133.30 nm, with an approximate polydispersity index (PDI) was 0.20 , a zeta potential was in the range of -32.50 to -26.53 mV. GA-DA-CH-Lips were constructed with more than 90% encapsulation efficient and drug loading efficiency of no<6.40%. In addition, envi-ronmental stability assays show that GA-DA-CH-Lips are sensitive to temperature, and thus should be preserved at low temperatures. Furthermore, in vitro cellular uptake from qualitative and quantitative analysis indicates that GA-DA-CH integrating into liposomes possess a specific target for hepatocellular carcinoma. Intracellular inhibition showed that GA-DA-CH-Lips effec-tively inhibited cell proliferation in dose-dependent features. Based on these results, we have reason to believe that GA-DA-CH-Lips could be a potential hepatic target drug delivery to improve the therapeutic effect of hepatic diseases.& COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).