The invention provides a nanocrystal composition of a slightly-soluble antitumor drug, i.e., camptothecin and derivatives thereof, and a preparation method thereof. According to the invention, an optimized alkali-dissolution acid-precipitation high-pressure-homogenization process is employed; drug powder is subjected to alkali dissolution and then acid is added at a gradient speed to allow a nanocrystal to be precipitated; acid precipitation is carried out in two steps, and a produced salt is removed through a centrifugation step; and high-pressure homogenization is carried out to further decease a particle size. Preferably, the camptothecin nanocrystal has an average particle size of 100 to 150 m and is uniformly distributed; the camptothecin nanocrystal can be preserved for a long time in the form of freeze-drying powder only by adding a minute quantity of poloxamer 188 as a freeze-drying protection agent; and in use of the camptothecin nanocrystal, a glucose solution with a concentration of 5% is added and shaken out, so the camptothecin nanocrystal directly recovers to a state before freeze-drying. The method is simple, good in repeatability and suitable for large-scale production. The prepared nanocrystal has good slow release effect; and compared with commercially available injections, the nanocrystal has prolonged circulation time in blood plasma, improves distribution of the drug in human tissue and has beeter antineoplastic effect and good development prospects.