Thyroid cancer is a common endocrine malignancy. The last decade has seen exciting progress in understanding thyroid cancer molecular pathogenesis. Several major signaling pathways and related molecular derangements have been elucidated, which represent novel diagnostic and prognostic molecular markers for thyroid cancer. Based on the molecular biology of thyroid cancer, a series of therapeutic targets have been developed, which provide unprecedented opportunities. Thus, histological characterization of subgroups of patients and the correct molecular characterization of patients are thought to be key aspects for future clinical management of these patients. In the present study, we identified Slit2 as a prognostic marker for thyroid cancer oncogenesis and recurrence. Mechanistically, Slit2 regulated Warburg effect in thyroid cancer cells through regulation of HIF1α and HIF1α transcriptional activity. Taken together, our present data uncovered Slit2 as a novel predictive marker for thyroid cancer. The mechanism study indicated that Slit2 regulated the Warburg effect. Additional study on the function of Slit2 in thyroid cancer is required to provide new insights into the potential mechanisms of oncogenesis and recurrence potential of thyroid cancer.