<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The aim of the study was to determine the human leucocyte antigen class-I (HLA-I), programmed death-ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) of microsatellite instability-high gastric cancer.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>The HLA-I expression type was determined by immunohistochemistry of HLA-A, HLA-B, HLA-C and β2-microglobulin in the centre of the tumour (CT) and in the invasive margin (IM) of samples from 293 patients (total loss vs. preserved type). PD-L1 expression and TIL density was examined immunohistochemically. HLA-I genotyping was also performed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The expression loss of the HLA-I molecules was significantly associated with low TIL density. According to survival analyses, the HLA-I expression type and PD-L1 positivity were not independent prognostic factors. The TIL density had no prognostic implication when survival analysis was performed for the whole patient group; however, high CD8<jats:sup>+</jats:sup> TIL infiltration was significantly associated with good prognosis in only HLA-I-preserved-type/PD-L1-positive group (<jats:italic>p</jats:italic> = 0.034). The homozygosity of the HLA-I allele was more frequently observed in the total loss type group.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We confirmed differential prognostic implication of CD8<jats:sup>+</jats:sup> TILs according to the HLA-I and PD-L1 expression. Determination of the HLA-I expression could be helpful to select patients who would benefit from anti-PD-1/PD-L1 therapy.</jats:p> </jats:sec>