We established the first regulatory network of TF‐miRNA‐target gene for the progression of COAD, involving 144 TFs, 26 miRNAs, and 7 hub genes, such as model KLF11‐miR149‐BGN, TCEAL6‐miR29B2‐COL1A1, and TCEAL6‐miR29B2‐COL1A2. This evidence concerns the gene KLF11 and colon adenocarcinoma.