In this study, we first constructed an A549 cell line with differential expression of NRP1 in vitro, and established a 2D or 3D co-culture system to mimic the in vivo microenvironment, and then further validated the 3D tumor model by constructing a mouse tumor-bearing model in vivo to study the role of NRP1 in radiation-induced lung cancer cell radiation resistance in inflammatory and migratory microenvironments. This evidence concerns the gene NRP1 and lung cancer.