Background: Thyroid malignancy is the most frequent endocrine malignant tumor whose incidence is still increasing. Mechanisms genomic variations play a major part in the pathogenesis of many types of malignancy. Synaptotagmin 12 (SYT12) is a member gene of the synaptotagmins family and SYT12's variants were shown to be associated with some malignancies. Nevertheless, SYT12's specific function and probable clinical value in papillary cancer were still unknown. Methods: We conducted complete genome sequence of 39 pairs PTC malignant neoplasm and matched non-neoplastic tissues. We found that SYT12 was significantly overexpressed in thyroid malignancy. Next, we investigated the expression level of SYT12 and the relation between clinical information and SYT12 expression in thyroid cancer in the Cancer Genome Atlas (TCGA). QRt-PCR of else 40 pairs local verified cohort was performed to confirm the sequencing data and TCGA cohort. Then, we used small interfering RNA (si-RNA) to knock down the expression of SYT12 in PTC cells. Finally, proliferation, cell colony formation, migration, invasion, and apoptosis assays were done to demonstrate the function of SYT12. Results: SYT12 is significantly overexpressed and higher expression of SYT12 upsurges the risk of lymph node metastatic and incidence rate of primary neoplasm multivariate focus type and classical histological type for PTC patients in TCGA cohort. In vitro experiments, the results of functional assays presented that knock-down of SYT12 inhibited the cell proliferation, cell colony formation, trans-well migration, and trans-well invasion and promoted cell apoptotic in PTC cell lines. Conclusion: SYT12 was a novel oncogene that promotes thyroid carcinoma progression and metastasis potential and a potential biomarker for diagnosis and treatment in PTC.