The invention relates to a preparation method of cefathiamidine, which comprises the following steps: (1) preparing cefathiamidine acid, performing silanization of 7-AC by BSA at room temperature, reacting with bromoacetyl bromide at zero DEG C, processing and separating out solid, filtering and drying to obtain high-purity cefathiamidine acid; (2) adding alkaline reagent to the cefathiamidine acid, reacting with N, N'-diisopropyl thiourea, adding slightly soluble solvent and separating out coarse cefathiamidine; and (3) dissolving the coarse cefathiamidine in a proper solvent, regulating the pH value of the solution to be between 4 and 5.5, adding the lightly soluble solvent until the solution is turbid, controlling the stirring speed, continuing slowly dripping the slightly soluble solvent, separating out the product, separating and drying to obtain the cefathiamidine. The method has the advantages of few steps, simple process, high purity and easy implementation.