Based on WGCNA, univariate cox regression survival analysis and Lasso analysis, we established a PLEGs model (including TWISTNB, ESPL1, TOPBP1, CPSF3, UBA1, and SEC61A1) screened from these proliferation essential genes, and this model could divide colon cancer patients into the low-risk group and high-risk group. The gene discussed is ESPL1; the disease is malignant colon neoplasm.