Background: Clinical trials suggested that solid tumors with MSI-high or dMMR are associated with responses to programmed cell death 1 inhibitors. Understanding the associations of MMR status with clinicopathological characteristics in CRC patients would help further guide clinical treatment and explore the pathogenetic mechanisms of this disease. Methods: Bioinformatics analysis was used to identify the differential expression genes between CRC patients with different MMR status. 208 resectable colorectal cancer patients, including 104 dMMR patients and 104 matched pMMR patients were retrospectively analyzed. Clinicopathological data, including age, gender, tumor location, histological subtype, tumor grade, tumor stage, regional lymph node (LNs) metastasis, American Joint Committee on Cancer (AJCC) 8th edition stage, perineural invasion, vascular invasion, number of retrieved LNs, number of metastatic LNs, systemic inflammation markers, including C-reactive protein (CRP), lactic dehydrogenase (LDH), albumin, neutrophil, monocyte, lymphocyte, platelet and survival were retrospectively reviewed. Results: Bioinformatics analysis shown chemokine-mediated signalling pathway and inflammatory response were the main differences in gene expression between dMMR and pMMR CRC patients. In all 208 CRC patients, those with dMMR were more frequently located in right side, with more mucinous adenocarcinoma, and with more grade 3 for tumor grade. Patients with dMMR had earlier AJCC stage than pMMR ones. Meanwhile, lymph nodes (LNs) metastasis was more frequently in dMMR patients compared with pMMR patients. Interestingly, CRC patients with dMMR were able to remove more regional lymph nodes during surgery, but with less metastati. Resectable CRC patients with dMMR were more likely to have higher level of neutrophil, monocyte, platelet, NLR, PLR, MLR, CAR, GPS and CRP. In CRC patients with dMMR, the patients with higher level of PLR, MLR, CAR and co-effect present had shorter OS significantly. It was interesting to note that the prognosis of high level of systemic inflammatory markers did not predict long OS in pMMR CRC patients. Conclusions: dMMR CRC has presented a comprehensively distinct systemic inflammatory microenvironment. The systemic inflammatory response can predict oncological outcomes in CRC patients with dMMR.