Background: Tumors expressing programmed death ligand 1 (PD-L1) can render immune inactivated via triggering of PD-1 receptor on T cells with various pathways. Based on this mechanism, the blockade PD-1/PD-L1 pathway has been used as a therapeutic target for metastatic CRC. In the present study, we evaluated the prognostic role of PD-L1 expression associated with microsatellite status in surgically resected stage III colon cancer patients. Methods: PD-L1 expression was performed by immunohistochemistry from 182 stage III colon cancer patients after curative resection. The percentage of PD-L1 positive tumor cells and staining intensity were evaluated and categorized as ‘strong’ or ‘weak’ positive group. Clinical and histopathologic parameters including of MSI status and survival outcomes were analyzed with IDO expression which stands for the suppressive immune environment. Results: Strong PD-L1 expression was observed in 29% of all patients. Perineural invasion and lymphocyte response were more frequently shown in strong expression of PD-L1 grop. Among resected patients, MSI was shown in 23 patients (12%). Although there was no significant difference between microsatellite status and PD-L1 expression, strong PD-L1 tended to better overall survival in microsatellite stable (MSS) colon cancer (P = 0.056). In contrast, strong PD-L1 expression was significantly correlated with worse DFS (P = 0.001) and OS (P < 0.001) than weak PD-L1 expression group in microsatellite instability (MSI) patients, regardless of adjuvant chemotherapy. Also, the strong IDO expression was tended to be more frequently shown in strong PD-L1 expression (36.4%) group than weak PD-L1 expression (14.3%) group in MSI patients. Conclusions: The expression of PD-L1 is differently affected on the survival outcomes according to the status of microsatellite. There is no significant relationship between the expression of PD-L1 and prognosis in MSS stage III colon cancer patients. However, in MSI colon cancer which has been well known as a highly immunogenic property, strong PD-L1 expression is significantly associated with poor prognosis on survival outcomes reflecting the immunosuppressive microenvironment in curative resected stage III colon cancer patient. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.