The incidence of colon cancer is amongst the top three in the world. The tumour microenvironment plays an important role in the occurrence and development of colon cancer. Stromal cells and immune cells are the main components of the tumour microenvironment. Our study detected genes, which affected the infiltration of stromal, immune cells and the way they affected the prognosis of colon cancer patients. We found that the colon's immune system had a special way to affect the tumour microenvironment. Moderate infiltration of stromal and immune cells was proved to be important protective factors for colon cancer patients, which has not been found in other tumours. C3, C5, CXCL12, GNAI1, LPAR1, PENK, PYY, SAA1 and SST were the differential expression hub genes of moderate-stromal and immune score group. They had a more significant correlation with tumour purity and infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophage, neutrophil, democratic cells. The proteins encoded by C3, C5, CXCL12, GNAI1, PENK, PYY, SST were detected in colon cancer cells. These genes had the potential to become markers to predict the prognosis of patients with colon cancer.