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Background: Head and neck squamous cancer (HNSC) frequently occurs in the clinic. Revealing the role of the genes that correlate with cancer cell outgrowth will contrib-ute to potential treatment target identification and tumor inhibition.Methods: The gene expression profiles and gene ontology of the proton-sensing G-protein-coupled receptor OGR1 were analyzed using the TCGA (The Cancer Genome Atlas) database. The effects of sex, age, race, and degree of malignancy on HNSC were investigated, and the survival times of HNSC patients with high or low/medium expression levels of OGR1 were compared. Methylation of the OGR1 pro-moter CpG sites was also investigated and OGR1-related genes were analyzed using gene set enrichment analysis. Results: OGR1 is overexpressed in HNSC patients. However, compared with the low/median expression group, the high OGR1 expression group did not have dif-ferent survival rates. The OGR1 expression level differed across sex, age, race, and degree of malignancy, while the methylation of the OGR1 promoter CpG sites was maintained at a similar level. Gene set enrichment analysis revealed that OGR1 was positively correlated with head and neck cancer, cisplatin resistance, hypoxia, angio-genesis, cell migration, and TGF-β. Conclusion: The expression of OGR1 correlated with HNSC progression and survival and thus can serve as a potential treatment target and prognostic marker.