The invention discloses a preparation method of vernakalant hydrochloride. The preparation method comprises the following steps: (1) adding a substrate (1R, 2R)- 2- (3, 4-dimethoxyphenethoxy) cyclohexylamine into a solvent; (2) adding an alkaline reagent, and controlling the temperature of the system; (3) adding an epoxy compound, controlling the temperature of the system, and raising the temperature to carry out cyclization reaction for a period of time; and (4) filtering to obtain a vernakalant solution, adding a hydrochloric acid solution to salify, concentrating under reduced pressure, andadding a crystallization solvent to crystallize, thereby obtaining the vernakalant hydrochloride. According to the invention, a chiral epoxy compound is adopted for cyclization reaction, the characteristics of high yield, short reaction time, simplicity and convenience in operation, mild conditions, convenience in post-treatment, easiness in industrial production and the like are realized, the use of heavy metals is avoided, and the development of injection medicines is facilitated.