Thyroid cancer (TC) is the most common endocrine malignancy, with high incidence rates in recent decades. Most TC cases have good prognoses, but a high risk of recurrence and metastases poses challenges, especially for patients with high-risk factors. Currently used prognostic markers for TC involve a combination of genetic factors and overexpressed proteins. Long non-coding RNAs (lncRNAs) regulate several integral biologic processes by playing key roles in the transcription of several downstream targets maintaining cellular behavior. Prior studies have revealed that lncRNAs promote tumor cell proliferation, invasion, metastasis, and angiogenesis, making them important targets for therapeutic intervention in cancer. While the exact molecular mechanisms underlying the role of lncRNAs in modulating TC progression and recurrence is still unclear, it is important to note that some lncRNAs are upregulated in certain cancers, while others are downregulated. In the present study, we review several key lncRNAs, their association with cancer progression, and the important roles they may play as tumor suppressors or tumor promoters in tumorigenesis. We discuss the potential mechanisms of lncRNA-mediated pathogenesis that can be targeted for the treatment of TC, the existing and potential benefits of using lncRNAs as diagnostic and prognostic measures for cancer detection, and tumor burden in patients. 2021 Annals of Translational Medicine. All rights reserved.