A series of novel supramolecular organocatalysts of hydroxyprolinamide based on the upper rim of calix[4]arene scaffold have been developed to catalyze enantioselective multi-component Biginelli reaction. Under the optimal conditions, the reactions occurred with moderate-to-excellent enantioselectivities (up to 98% ee). A plausible transition state constructed by the supramolecular interaction of hydrogen bond and cation- between catalysts and substrates has been proposed. supramolecular organocatalyst, calix[4]