Lung cancer ranks among the most prevalent malignant tumors, characterized by delayed diagnosis, limited treatment efficacy, and generally poor prognosis. Consequently, there is an urgent demand for effective treatments. Neoantigen-based immunotherapy emerged as a promising strategy in lung cancer treatment as ideal targets for immunotherapy interventions. Neoantigens are tumor-specific antigens produced by genetic mutations in somatic cells, which, unlike tumor-associated antigens, are found only in tumor tissue. Neoantigen immunotherapy has the advantages of high specificity, high safety and low immunotolerance, especially for lung cancer patients with a high tumor mutation load. We systematically summarize the biological characteristics, prediction and identification, mechanism of action, clinical application, risk challenges, and prospects of neoantigens as a novel precision immunotherapy method in lung cancer to provide valuable insights and references for the advancement of lung cancer treatment strategies.