The invention discloses a preparation method of novel selenium-rich drug-loading microspheres. The preparation method comprises the following steps: dissolving polylactic acid in methylene chloride, and uniformly dispersing barium selenite in the solution to form an emulsion; injecting the emulsion into a polyvinyl alcohol solution while stirring to form an S/O/W type emulsion; stirring to volatilize dichloromethane, and curing to form spheres; and performing centrifugal washing and drying to obtain the selenium-rich drug-loading microspheres. The selenium-rich drug-loading microspheres disclosed by the invention take barium selenite as a main drug, all components of the drug-loading microspheres are prepared by virtue of reasonable optimization, the drug-loading microspheres are prepared by adopting a coating process of S/O/W and using an emulsion solution volatilization method and are high in drug loading quantity, and the release speed of drugs is controlled by controlling process conditions, thereby reducing the usage amount of barium selenite, prolong the acting time of the drugs, reducing the toxic or side effect of the drugs and improving the curative effect of the drugs.