Thyroid cancer has been the fastest rising malignancy since the 20th century. Although the instance rates are continuously increasing, many clinical challenges around its pathogenesis, diagnosis, and prognosis are still waiting to be resolved. This research then adopts machine learning, specifically data mining and deep learning techniques, to help address the challenges and reveal the mystery around thyroid cancer. With the proposed algorithms and systems, the risk factors correlated with the disease were determined, and the comprehensive diagnosis was achieved in assisting clinicians to gain “second opinions” in the decision-making process, aiming for a promising prognosis for the target patient.