Background: Immune checkpoints are an emerging treatment target. Microsatellite instability (MSI), mutational load and checkpoint expression are imperfect predictors of treatment efficacy. We here describe a link between DNA repair gene methylation and expression of immune checkpoints in tumor tissue. Methods: A list of DNA repair genes (179 genes) was established from literature. mRNA expression and methylation status was extracted from TCGA data. Correlation analysis of DNA repair gene methylation status and expression of immune checkpoint gene mRNA was performed (cbioportal.org) in HNSSC (279 samples) and validated in other cancer types. Statistical analysis was carried out in R. Results: In HNSCC, methylation of 15 DNA repair genes was identified to be positively correlated to expression of PD-L1 and CTLA4 expression (cutoff: Spearman coefficient r > 0.3). Subgroup analysis revealed statistically significant enrichment for the homologous recombination pathway (p = 0.003). Methylation of candidate genes was associated with reduced expression. Among candidate genes, RAD51B and XRCC3 methylation showed the highest correlation with PD-L1 (r = 0.471, r = 0.472) and CTLA4 (r = 0.525, r = 0.616) expression (p values < 2.2x10^-16). Methylation of these DNA repair genes was associated with expression of other checkpoint (CD28, PD-1, TIM-3, LAG-3, VISTA, ICOS, BTLA), ligand (PD-L2, CD80/86), IFNg, MHC-class 1 and T-cell associated genes (FOXP3, CD8A). These findings could be reproduced in independent datasets of lung squamous and cervical carcinoma and, to various extents, also in non-squamous cancer histologies (e.g. melanoma, lung adenocarcinoma). Conclusions: We propose for the first time a link between DNA repair gene methylation and expression of immune checkpoints identified in HNSCC and validated for lung and cervical cancer with similar effects also seen in other cancer types. We hypothesize that homologous recombination deficiency (HRD) may be mediated by DNA repair gene hypermethylation and linked to an immune-evasive phenotype. Correlation of DNA repair gene methylation and clinical efficacy of checkpoint inhibitors should be investigated.