The invention belongs to the technical field of medicines, and particularly relates to indazole piperidine pyrimidine derivatives and a preparation method and application thereof. The indazole piperidine pyrimidine derivatives replace an acrylamide structure forming covalent bonds on the basis of retaining the pyrimidine mother ring of third generation EGFR inhibitors to obtain a class of non-covalent bond binding inhibitors. Drug activity test results show that the compounds have excellent in vitro inhibitory effect on human lung cancer H1975 cells. At the same time, the toxicity of most compounds to human normal cells is less than the toxicity of most compounds to lung cancer cells, better selectivity is shown, and the indazole piperidine pyrimidine derivatives can be used for further development of anticancer drugs.