The invention belongs to the field of organic chemical synthesis, and discloses cyclobutyl-1-enamine compounds, a preparation method thereof and application of the cyclobutyl-1-enamine compounds in antiviral and antitumor drugs. The compound has a structure of a general formula (I), and EWG is selected from alkyl or aryl substituted sulfonyl; r is selected from alkyl, alkoxy, halogen and nitryl. The preparation method comprises the following steps: heating an alkyne amide raw material to a molten state under thermal driving, and carrying out [2 + 2] cycloaddition reaction among molecules to obtain the polysubstituted cyclobutyl-1-enamine compound. The method has the advantages of easily available raw materials, simple steps, no catalyst, no solvent, high yield and the like. The compound has anti-SARS-CoV-2, 5637, Hela, SW480, Hep G2, A549 and MCF-7 activity, and has a good application prospect in the aspect of treating novel coronavirus, bladder cancer, cervical cancer, colon cancer, liver cancer, lung cancer and breast cancer. (I).