Cancers of the digestive system are malignant diseases. Our study focused on colon cancer, esophageal cancer (ESCC), rectal cancer, gastric cancer (GC), and rectosigmoid junction cancer to identify possible biomarkers for these diseases. The transcriptome data were downloaded from the TCGA database (The Cancer Genome Atlas Program), and a network was constructed using the WGCNA algorithm. Two significant modules were found, and coexpression networks were constructed. CytoHubba was used to identify hub genes of the two networks. GO analysis suggested that the network genes were involved in metabolic processes, biological regulation, and membrane and protein binding. KEGG analysis indicated that the significant pathways were the calcium signaling pathway, fatty acid biosynthesis, and pathways in cancer and insulin resistance. Some of the most significant hub genes were hsa-let-7b-3p, hsa-miR-378a-5p, hsa-miR-26a-5p, hsa-miR-382-5p, and hsa-miR-29b-2-5p and SECISBP2 L, NCOA1, HERC1, HIPK3, and MBNL1, respectively. These genes were predicted to be associated with the tumor prognostic reference for this patient population.