The invention relates to the technical field of chemical industry, in particular to a preparation method and application of micromolecule compound with HIV resisting activity. CyPA is able to combine with the Gag polymer protein in HIV-1. Silence or inhibit the activity of CypA with RNAi technology and disturb the replication of virus. The micromolecule compound in the invention refers to a CyPA inhibitor that has the effect of resisting HIV-1 virus. Besides, as the micromolecule compound is designed while aiming at cellular target, the invention is not easy to develop drug resistance, thus meeting the demands of lifetime medication for AIDS patients. Therefore, the micromolecule compound in the invention, which can be developed as a new type anti-AIDS drug, provides a new means for treating and curing AIDS.