Lung cancer has one of the highest morbidity and mortality rates. Non-small cell lung cancer is a subtype with a relatively high degree of malignancy and proportion. In recent years, immunotherapy for non-small cell lung cancer has become a research focus. Numerous immune monotherapies and combined therapies have emerged. The development of these therapies requires preclinical verification. Therefore, reliable animal models are needed to evaluate therapeutic effects, explore optimal drug regimens and promote individualized medical treatment. Because a xenotransplantation model with a humanized immune system has both a human immune system and human tumor cells, it closely recapitulates the tumor immune microenvironment in the human body, which has a broad application prospect in the research of oncological immunotherapy. This article mainly reviews the application of humanized models and provides guidance for preclinical trials of various immunotherapy schemes for non-small cell lung cancer to promote clinical trials of these schemes.