SeMet/CS Nanocomposite microspheres were prepared using SeMet as a core material and chitosan(CS) as a wall material using emulsion crosslinking. The work in this paper focused on the indicators of microspheric form, drug-loading rate, entrapment efficiency and slow-release property using the single-factor and orthogonal test to optimize the preparation technology. During the processes, a scanning electron microscope, a Fourier infrared spectrometer, a thermal analyzer and double-channel atomic fluorescence were applied for detection, analysis and characterization. Furthermore, in vitro tests, such as for the selenium-releasing property and anticancer activity, were studied for the prepared selenium microsphere. The data indicated that the SeMet/CS microsphere prepared under the optimum conditions of 0.1% dosage and 2% dosage of crosslinking agent were crosslinked at 50℃ for 10 min. The obtained SeMet/CS microspheres exhibited superior features, with an Excellent morphology and an embedding ratio and drug loading of 31.94% and 0.59%, respectively. They displayed excellent sustained-release capability in an SBF model. Regarding anticancer activity, they showed a significant inhibitory effect on MCF-7 human breast cancer cells, and there was a positively correlated between the inhibition rate and the content of selenium in the sustained-release liquid. The SeMet/CS microsphere can effectively avoid a burst effect for selenium, allowing a controlled selenium dose. Thus, it can be used in selenide or selenium supplements for further application in medical, food and fine chemical industries.