The invention relates to the technical field of medicinal chemistry and in particular discloses a method for preparing benzisoxazole in one pot based on 2-hydroxyacetophenone oxime and derivatives thereof. The preparation method is as follows: under microwave or oil bath heating conditions, in an organic solvent, one-pot inversion is carried out on 2-hydroxyacetophenone oxime and derivatives thereof to form benzisoxazole compounds by utilizing a fluorine-containing accelerator and alkali. The method for synthesizing benzisoxazole has the advantages that raw materials are rich in source and easy to get, synthetic steps are short, the operation is simple and convenient, the product yield is high, and the highest yield is 93%. A benzisoxazole structure exists in multiple drug molecules, so that the novel one-pot synthesis method disclosed by the invention has potential practical values.