The invention discloses a pleuromutilin derivative containing a 1, 2, 4-triazole acrylamide side chain as well as a preparation method and application of the pleuromutilin derivative, and belongs to the field of medical chemistry. According to the compound, pleuromutilin and different substituted acrylic acid are used as raw materials, 3-sulfydryl-1, 2, 4-triazole is used as a connector under the action of a catalyst, and the pleuromutilin derivative which is not reported, has the activity of resisting drug-resistant bacteria and contains a 1, 2, 4-triazole acrylamide side chain is synthesized. The synthesis method is high in operation safety, mild in reaction condition and suitable for industrial production. Preliminary biological activity tests and safety evaluation show that the pleuromutilin derivative containing the 1, 2, 4-triazole acrylamide side chain and having the drug-resistant bacterium resisting activity has good drug-resistant bacterium resisting activity and safety, so that the pleuromutilin derivative can be applied to treatment of infectious diseases, especially infectious diseases caused by drug-resistant bacteria, and has good application prospects. The medicine development value is very good.