The invention discloses a chemical synthesis method of valnemulin hydrochloride, which comprises the following steps of: taking refined pleuromutilin as raw material, carrying out sulfonation by paratoluensulfonyl chloride, and reacting with dimethyl cysteamine hcl, to obtain the pleuromutilin dimethyl cysteamine substitute; reacting D-valine, methyl acetoacetate and potassium hydroxide to obtain (R)-2-(1-methoxycarbonyl group-2-allyl) amino-3-methyl potassium butyrate, activating by ethyl chloroformate and reacting with the pleuromutilin dimethyl cysteamine substitute, adjusting PH value, carrying out reverse phase extraction, and carrying out freeze-drying to obtain the valnemulin hydrochloride. The method has the advantages that due to the refining of the raw material pleuromutilin, the impurities in the product can be effectively removed, and the purifying process can be simplified from the source; the carboxyl of D-valine can be activated by the ethyl chloroformate, so that the reaction is easier to carry out; and due to the pH adjustment, the reverse phase extraction, and the freeze-drying, the product can be obtained, so that the product is stable in quality, and high in purity.