Background: Glucagon like peptide-1 receptor (GLP-1R) agonist usage has previously been linked to an elevated incidence of thyroid cell adenomas and carcinomas in animals. Aim: The goal of this study was to determine if there was an association between GLP-1R gene polymorphism and expression with the risk of papillary thyroid carcinoma (PTC) and its clinical characteristics among the Egyptian population. Material and methods: A total of eighty PTC patients and eighty healthy controls were included in the study. Real- time polymerase chain reaction (real-time PCR) and immunohistochemistry were used to determine GLP-1R expression in tumor tissue. The polymorphisms rs1042044 and rs6923761 in the GLP-1R gene were deter mined using PCR -restriction fragment length polymorphism (PCR-RFLP). Results: PTC patients exhibited considerably greater frequencies of rs1042044 AA genotypes and A allele than controls (OR (95% CI) = 4.5 (1.75–11.8), P < 0.001; OR (95% CI) = 2.032 (1.301–3.17), P < 0.001 respectively). GLP-1R mRNA and protein expressions were higher in tumor samples than normal thyroid tissues among PTC patients. In addition, high GLP-1R expressions were more common in rs1042044 AA genotype carriers than CC carriers (P < 0.001). GLP-1R mRNA expression showed 95 % sensitivity and 97% specificity for PTC diagnosis. Moreover, GLP-1R expression was closely associated with LN metastasis, tumor size, tumor stage, and multi focality in PTC patients. Conclusion: This research provides new evidence linking the GLP-1R genetic polymorphism and tissue expression to PTC risk and invasiveness among the Egyptian population.