In order to treat coal slime-water, the crosslinked cationic starch flocculant was prepared in this paper. The prepared samples were characterized and analyzed by Scanning Electron Microscope (SEM), X-ray diffraction spectroscopy (XRD) and Fourier transform infrared spectroscopy (FT-IR), and the effect of various factors on the flocculation performance of coal slime-water was investigated using coal slime-water as the test object. The results showed that the methacryloyloxyethyl trimethyl ammonium chloride (DMC) and 2,3-epoxypropyl trimethyl ammonium chloride (GTA) were successfully synthesized on the starch backbone and the cationic starch was crosslinked successfully. Compared cross-linked cationic starch and commercially available anionic (cationic) polyacrylamide, the results showed that the cross-linked cationic starch has low turbidity, wide pH range, high floc compression rate and low cake moisture content when treating coal slime-water. The EDLVO theory was used to analyze the excellent flocculation performance of cross-linked cationic starch flocculants on coal slime-water.