Thyroid cancer (THCA) is a common endocrine malignant tumor, and its global incidence of THCA has increased significantly. Neurexin 2 (NRXN2) is involved in the progression of some diseases. Nevertheless, it is still elusive towards the clinical implication and function of NRXN2 in THCA. As The Cancer Genome Atlas (TCGA) data demonstrated, we conducted a study to explore the links between NRXN2 expression and clinical features. Additionally, our data exhibited that, compared to normal thyroid tissues, NRXN2 showed low expression in THCA tissues. 20 important genes associated with NRXN2 were screened and identified. KEGG analysis data displayed that NRXN2 exhibited a link to the neuronal system, insulin secretion modulation, energy metabolism integration, muscle contraction, cardiac conduction, and neural adhesion molecule 1 (NCAM1) interactions. Our results in depth affirmed that NRXN2 was decreased in the tissues and cell lines of THCA patients. Functionally, we proved that overexpressing NRXN2 resulted in an inhibition of THCA cell proliferation, migration, and invasion in vitro. Collectively, our study demonstrated that, for the first time, NRXN2 behaved as an inhibitor of neoplasm and a promising biomarker in THCA.