The invention discloses a preparation method of a hydrochloric acid ciprofloxacin lipidosome preparation. The preparation method includes the steps that one part of hydrochloric acid ciprofloxacin is weighed, a phosphate buffer solution is added and stirred, and a hydrochloric acid ciprofloxacin solution is obtained; 2, blank liposome is prepared, wherein 10-50 parts of soya bean lecithin and 5-40 parts of cholesterol are weighed and mixed, chloroform is added and stirred for being dissolved, decompression is conducted for removing solvent, and a blank phospholipid membrane is prepared; 3, the membrane is dissolved through a small amount of chloroform, the hydrochloric acid ciprofloxacin solution obtained in step 1 and the phosphate buffer solution are taken for being added into an acetate solution, ultrasound treatment is conducted for 10-30 minutes through a bath type ultrasonic instrument at the temperature of 45-60 DEG C, a stable solution is formed, the obtained lipidosome solution is filtered twice through a microfiltration membrane, granulation is conducted, and the hydrochloric acid ciprofloxacin lipidosome preparation is obtained. The lipidosome produced through the ultrasonic instrument has the advantages that the particle size is small, particle size distribution is narrower, and the lipidosome has good preparation nature and target ability, can improve the curative effect, has a long-term effect, can reduce drug toxicity and can improve the drug stability.