Background: GC is a heterogeneous disease with a range of molecular subtypes. The TCGA (Cancer Genome Atlas) and ARCG (Asian Cancer Research Group) classified tumors with MSI status as a specific group. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) are playing a progressively important role in tumor immunology and cancer treatment. The present study investigated the relationship between MSI and PD-L1 expression. Methods: We analyzed GC patients who received treatment from September 2019 to March 2023 at N.N. Blokhin National Medical Research Center of Oncology. All patients were analyzed for microsatellite instability using PCR. PD-L1 expression was assessed based on a combined positive score (CPS) using PD-L1 IHC (immunohistochemistry) 22C3 pharmDx. Results: We studied 453 localized GC and 273 metastatic GC. Of the 726 tumors, 60 (8.26%) had MSI-H tumors. The frequency of MSI-H in localized and metastatic GC is 51 (11.26%) out of 453 and 9 (3.30%) out of 273 (p<0.001). 106 patients were evaluated for expression PD-L1, 46 (43.40%) localized GC и 60 (56.60%) metastatic GC. PD-L1 is expressed in 45.28 % (48/106) of GC patients. PD-L1 CPS ≥ 1 was significantly associated with MSI-H status (P < 0.05). Details about the correlation between MSI and the expression PD-L1 can be found in the table. Conclusions: The prevalence of MSI-H in localized GC is significantly higher than metastatic GC (11.26% vs. 3.30%, p<0.001). A higher proportion showed PD-L1 expression (73.91%) in MSI-H than in MSS tumors, suggesting that MSI-H status is associated with PD-L1 (p< 0.05). These results provide a basis for identifying GC patients who may benefit from anti-PD-1/PD-L1 therapy.