BACKGROUND: The microsatellite status (dMMR vs. pMMR) in colorectal cancer can serve as a guiding factor for patient prognosis and treatment, where dMMR status indicates a better prognosis and often obviates the need for adjuvant chemotherapy (ACT). Conversely, a higher lymph node ratio (LNR) is associated with a poorer prognosis. This study aims to elucidate the prognostic significance of LNR and MMR status in relation to ACT in stages II and III colorectal cancer. METHODS: A total of 1946 patients who underwent radical resection for colorectal cancer and were pathologically staged as II and III from three medical centers between 2012 and 2019 were selected. Among them, 1104 patients were included after MMR status was tested and postoperative chemotherapy was administered, along with other clinical information. MMR (mismatch repair) status was determined via pathological immunohistochemistry (IHC), and LNR was calculated. Patients were divided into three groups based on the LNR value and subjected to Kaplan-Meier and Cox regression analysis to assess the impact of MMR, LNR, and ACT on overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 6.47% of stage II and III colorectal cancers were detected as dMMR. Significant differences in OS and DFS between dMMR and pMMR patients were observed when the LNR ranged from 0.03 to 0.31, with pMMR patients showing a better prognosis. Stratified analysis with ACT revealed that postoperative chemotherapy did not affect the prognosis within the dMMR patient group. However, compared to the pMMR group, dMMR patients experienced significantly adverse effects on prognosis after receiving postoperative chemotherapy (p < 0.05). This result was more pronounced in the stratified analysis based on LNR (0.03-0.31) (p < 0.01). CONCLUSIONS: Integrating LNR based on the microsatellite status of colorectal tumors provides comprehensive prognostic predictions, enhancing postoperative prognostic considerations for tumor patients. Additionally, our study suggests that patients with stage II and III colorectal cancer with dMMR status do not require any adjuvant chemotherapy postoperatively.