Cholesterol-enhanced　pore　formation　is　one　evolutionary　means　cholesterol-free　bacterial　cells　utilize　to　specifically　target　cholesterol-rich　eukaryotic　cells,　thus　escaping　the　toxicity　these　membrane-lytic　pores　might　have　brought　onto　themselves.　Here,　we　present　a　class　of　artificial　cholesterol-dependent　nanopores,　manifesting　nanopore　formation　sensitivity,　up-regulated　by　cholesterol　of　up　to　50　mol%　(relative　to　the　lipid　molecules).　The　high　modularity　in　the　amphiphilic　molecular　backbone　enables　a　facile　tuning　of　pore　size　and　consequently　channel　activity.　Possessing　a　nano-sized　cavity　of　~　1.6　nm　in　diameter,　our　most　active　channel　Ch-C1　can　transport　nanometer-sized　molecules　as　large　as　5(6)-carboxyfluorescein　and　display　potent　anticancer　activity　(IC50　=　3.8　µM)　toward　human　hepatocellular　carcinomas,　with　high　selectivity　index　values　of　12.5　and　>130　against　normal　human　liver　and　kidney　cells,　respectively.　©　2022,　The　Author(s).