A novel multifunctional liposomal delivery platform has been developed to resemble the structural and functional traits of an influenza virus. Novel pseudopeptides were prepared to mimic the pH-responsive endosomolytic behavior of influenza viral peptides through grafting a hydrophobic amino acid, l-phenylalanine, onto the backbone of a polyamide, poly(l-lysine isophthalamide), at various degrees of substitution. These pseudopeptidic polymers were employed to functionalize the surface of cholesterol-containing liposomes that mimic the viral envelope. By controlling the cholesterol proportion as well as the concentration and amphiphilicity of the pseudopeptides, the entire payload was rapidly released at endosomal pHs, while there was no release at pH 7.4. A pH-triggered, reversible change in liposomal size was observed, and the release mechanism was elucidated. In addition, the virus-mimicking nanostructures efficiently disrupted the erythrocyte membrane at pH 6.5 characteristic of early endosomes, while they showed negligible cytotoxic effects at physiological pH. The efficient intracellular delivery of the widely used anticancer drug doxorubicin (DOX) by the multifunctional liposomes was demonstrated, leading to significantly increased potency against HeLa cancer cells over the DOX-loaded bare liposomes. This novel virus-mimicking liposomal system, with the incorporated synergy of efficient liposomal drug release and efficient endosomal escape, is favorable for efficient intracellular drug delivery.