The invention discloses a florfenicol supermolecule preparation and a preparation method thereof. The preparation is prepared from the following raw materials in parts by weight: 5-10 parts of florfenicol, 5-20 parts of soybean protein isolate, 5-20 parts of maltodextrin, 10-40 parts of ethyl alcohol-purified water with the mass ratio of 1 to 1, and 20-80 parts of one or several of glucose, cane sugar with particle diameter of 80 meshes, or HPMC (Hydroxypropyl Methylcellulose). The preparation technology comprises the steps as follows: firstly, the soybean protein isolate and the maltodextrin are mixed into graft polymer of the soybean protein isolate and the maltodextrin as a supermolecule object; secondly, obtained florfenicol emulsion is put into a reaction kettle so as to be subjected to ultrasound for 30-60 minutes, and supermolecule micro emulsion is formed with florfenicol molecules being embedded in the graft polymer object of the soybean protein isolate and the maltodextrin, and dried; thirdly, after the drying, auxiliary materials are put in additionally for obtaining the preparation. The florfenicol supermolecule preparation obtained through the method provided by the invention is high in bioavailability, simple, convenient and economic in technology, high in production efficiency, safe and environmental-friendly, and good in reproducibility; moreover, the obtained products can be mixed with feeds or be mixed with drinks, and the preparation is convenient for pharmacy, and can be mixed with feeds or water, thereby receiving welcome from the majorities of farmers deeply.