Diffuse-type gastric cancer (DGC) is a gastric cancer subtype based on Laurén histological type, with poor prognosis when compared intestinal-type gastric cancer. It is necessary that comprehensive analysis identifies pathways and genes involved in DGC. RNA expression data of DGC (including 52 samples, top 5000 genes) and fourteen patient clinic traits were downloaded from The Cancer Genome Atlas (TCGA) database. Co-expression modules and module-trait relationships were constructed by weighted gene co-expression network analysis (WGCNA). The identified ten co-expression modules were obtained from DGC samples. The co-expression turquoise module positively correlated with longest dimension. The co-expression magenta module positively correlates with gender, and person neoplasm cancer status. The co-expression green module also positively correlates with pathologic N stage and pathologic stage. Besides, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment obtained some cancer related signal pathways in the co-expression turquoise and green module, such as proliferation, drug resistance, cell metabolism. Additionally, we identified the hub genes in the co-expression turquoise, green and magenta modules. Protein-protein interaction (PPI) and biological processes (BP) analysis were performed on the hub genes in those modules, suggesting the key role of those modules in the development of the cancer. The hub genes were significantly related to Overall survival analysis showed some important hub genes were significant in DGC patients, including ANK2, GNAO1, MAP6, RERG (turquoise module), MEP1A, GUCY2C, ALDOB (green module), XIST, TTTY15, NCRNA00185, CYorf15B (magenta module). The study provided new biomarkers and potential mechanisms in DGC.