To enhance the stability of liposomes in systemic circulation, a number of liposomes modified with hydrophilic polymer such as poly(ethylene oxide) have been developed. In this study, the comb-type copolymer was prepared as a surface modifier of liposome and the polymer was anchored onto the lipid bi-layer via hydrophobic interaction between aliphatic chain of phospholipids and hydrophobic chain of the polymer. The comb-type copolymer was synthesized by radical polymerization of octadecyl acrylate (ODA), hydroxy-poly-(oxyethylene) methacrylate (HPOEM) and 2-Hydroxyethyl methacrylate (HEMA). The structure of the comb-type copolymer was confirmed by 1H-NMR analysis. The stability of the comb-type copolymer-incorporated liposomes (CCIL) in serum was investigated by measuring the amount of protein adsorbed onto liposomes. The CCIL showed a much lower amount of adsorbed protein than the other liposomes. Those results indicated that the stability of CCIL in serum was higher than those of the other liposomes. Thus, the comb-type copolymer composed of ODA-HPOEM-HEMA can be a promising surface modifier for enhancement of the stability of liposomes in systemic circulation.