The invention relates to a self-assembly system based on hydrophilic polymer and medicine and a preparation method thereof. The system consists of a hydrophilic polymer and a carboxyl-containing medicine, wherein the hydrophilic polymer is polymine or beta-cyclodextrin modified polymine; and the carboxyl-containing medicine is selected from ibuprofen, ketoprofen, fenoprofen, flurbiprofene, oxaprozin, naproxen, indometacin, sulindac, etodolac, diclofenac, pontal, meclofenamic acid, flufenamic acid, tolfenamic acid, lumiracoxib, licofelone, diflunisal and aspirin. The system is prepared by dissolving the hydrophilic polymer in a certain amount of water, dissolving the medicine in a water soluble solvent, slowly adding the organic solution of the medicine into the aqueous solution of the polymer under the action of ultrasound, placing the mixed solution in a dialysis bag, dialyzing in deionized water with magnetic stirring, replacing the deionized water at certain time interval, filtering dislysate after 5 to 48 hours, cooling and drying.