BACKGROUND: Papillary thyroid carcinoma coexisting with rheumatoid arthritis is frequently observed in clinical patients, yet its pathogenesis has not been fully elucidated. This investigation sought to further explore the molecular underpinnings of these two diseases. METHODS: Gene expression profiles for thyroid papillary carcinoma and rheumatoid arthritis patients were obtained from the Comprehensive Gene Expression Database (GEO). Following the discovery of shared differentially expressed genes (DEGs) between these two conditions, three separate analyses were conducted. These included functional annotation, the establishment of a protein‒protein interaction (PPI) network and module, and the identification of hub genes via coexpression analysis. The final step involved the validation of target genes via clinical specimens. RESULTS: This study analyzed datasets from four GEO databases and identified 64 common DEGs. Functional enrichment analysis revealed that these genes are predominantly associated with pathways related to immunity and signal transduction. Protein‒protein interaction (PPI) network analysis revealed complex interactions among these differentially expressed genes and highlighted several genes that may play pivotal roles in shared pathological mechanisms, namely, CCR5, CD4, IL6, CXCL13, FOXM1, CXCL9, and CXCL10. CONCLUSION: Our study highlights the shared pathogenesis between papillary thyroid cancer and rheumatoid arthritis. Shared pathways and crucial genes could offer novel perspectives for subsequent investigations into the mechanisms of these diseases.