The invention belongs to the field of drug synthesis, and provides a preparation method of octylonium bromide. The preparation method of the octylonium bromide comprises the following steps: synthesizing methyl o-octyloxybenzoate from methyl salicylate as a starting material and n-bromooctane; carrying out de-esterification to obtain o-octyloxybenzoic acid; condensing the o-octyloxybenzoic acid with procaine hydrochloride under the condensation effect of ethyl chloroformate to obtain a compound N,N-diethyl-2-[4-(2-octylbenzamido) benzoyloxy] ethanamine; and then reacting the compound N,N-diethyl-2-[4-(2-octylbenzamido) benzoyloxy] ethanamine with methyl bromide to obtain the target compound octylonium bromide. The total yield is 48.3%, and the improved octylonium bromide synthesizing process is simple and convenient to operate, and is suitable for industrialized production.