The invention provides an alpha-substituted isochroman derivative and a preparation method thereof. The structural formula of the derivative is shown in the description. According to the method, hydroxyethyl-substituted arone is mixed with nitroalkane, the temperature is increased from the room temperature to 150 DEG C, a reaction is performed for 0.5-3 days, and the alpha-substituted isochroman derivative is prepared. The method has the advantages that no catalyst, oxidizing agent or solvent is needed, the reaction is efficiently completed in one step, the reaction condition is mild and efficient, and the operation is simple. The synthesized compound can be used as an important structural unit of drugs, active natural products and organic synthesis.