Already in the 1980s, a study (INT 0035 trial) showed that postoperative adjuvant chemotherapy (5-Fu in combination with leucovorin) clearly reduced the risk of postoperative recurrence, making adjuvant chemotherapy the standard of care for postoperative patients with Dukes stage C. In further subsequent studies, the combination of 5-Fu with calcium folinic acid (leucovorin) (5-Fu/LV) was found to be significantly superior to 5-Fu combined with levamisole in terms of both therapeutic efficacy and safety. This established the foundation of 5-Fu combined with calcium folinic acid in adjuvant chemotherapy for colon cancer, and numerous chemotherapy regimens have been generated. By 2000, it was agreed that adjuvant chemotherapy based on 5-Fu combined with calcium folinic acid should be routinely used for six months for patients with stage III colon cancer after surgery. For stage I patients, postoperative adjuvant chemotherapy was not needed because of the good surgical outcome and high five-year survival rate. The main controversy at that time was whether postoperative adjuvant chemotherapy was needed for stage II patients? A number of prospective studies and meta-analyses have previously provided evidence for both sides of the controversy, with studies on the opposite side finding that chemotherapy does not improve long-term survival in stage II patients and is therefore unnecessary; even though the results from the positive side of the study suggest that postoperative adjuvant chemotherapy can benefit stage II patients, the advantages are small. The representative QUASAR study found that postoperative adjuvant chemotherapy improved the survival of stage II patients by less than 5%. Taken together, we can see that in order to confirm a greater improvement in survival in stage II patients from adjuvant chemotherapy, the sample size of the study would have to be increased substantially, which posed many difficulties in clinical research. In addition, the regimens used in the clinical trials at that time were all 5-Fu-based chemotherapy regimens, and some new drug regimens are still being investigated, such as the ECOG 5202 study using lexadine in combination with bevacizumab, and it will take time to see whether the new drugs will be effective in stage II patients. Stage II patients with a number of independent risk factors for good outcomes in postoperative adjuvant therapy are referred to as high-risk factors, including: ① T4 stage tumors with adhesions to surrounding organs and infiltration; ② preoperative combined intestinal obstruction or bowel perforation; ③ intraoperative number of regional lymph nodes obtained <12; ④ postoperative pathological findings of the presence of vascular tumor plugs; ⑤ poorly differentiated tumors or mucinous adenocarcinoma. Therefore, it is recommended that patients with stage II colon cancer combining any of the above factors should receive postoperative adjuvant chemotherapy.