Complex diseases were generally affected by the interaction of multiple genes . Generally, the common influence of interaction in interacting genes could not only decrease the complex degree of biological network, but also benefit to explore meaningful biological information for the researchers, which further provide scientific basis for therapy and study of disease. Previous studies indicated that many interacting genes had similar or same effects, or involved in the same biochemical pathways. Therefore, the known key gene in an established interaction network of genes would be found easily, and the functions of interacting genes can be preliminary predicted and annotated based on this gene. In this study, NSCLC-related gene was searched from database OMIM, COSMIC, GAD and DisGeNET, then a network chart was established with the adoption of PPI data from STRING, followed by the shortest path analysis and Permutation test. There is a total of 385 genes whose Betweenness value was greater than 0 gained through Dijkstra's algorithm. Permutation test showed 103 genes whose Permutation FDR was less than 0.05. There was a strong correlation between these genes and NSCLC, which could be used in the subsequent analysis.