OBJECTIVE: Recent studies have corroborated that circular RNAs (circRNAs) as endogenous noncoding RNAs gain research interest in carcinogenesis, functioning as prognostic and diagnostic biomarkers and therapeutic targets. The present study is aimed to determine whether circRNAs could serve as prognostic and diagnostic biomarkers to predict thyroid carcinoma. MATERIALS AND METHODS: High-throughput sequencing analysis was conducted to detect circRNAs expression profile in thyroid cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) measurement was utilized to validate circRNAs expression in blood and tissue specimens. Kaplan-Meier method and receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess whether circRNAs could function as prognostic and diagnostic biomarkers of thyroid cancer. respectively. RESULTS: Hsa_circ_0124055 and hsa_ circ 0101622 as the most conspicuous biomarkers were significantly increased in tumor tissues and plasma of thyroid cancer patients. High hsa_circ_0124055 or hsa_circ_0101622 expression exhibited shorter overall survival. Our findings also provided strong evidence that plasma hsa_circ_0124055 (AUC = 0.836. 95% CI: 0.763-0.908. p<0.001) and hsa circ 0101622 (AUC = 0.805. 95% CI: 0.727-0.883, p<0.001) could be used as diagnostic markers for thyroid cancer, and hsa_circ_0124055 combined with hsa_circ_0101622 could provide a more powerful diagnostic value (AUC = 0.911, 95% CI: 0.859-0.962, p<0.001) than the use of hsa_ circ_0124055 or hsa_circ_0101622 alone. Furthermore, the knockdown of hsa_circ_0124055 or hsa_circ_0101622 exhibited a significant anti-proliferative and pro-apoptotic activity of thyroid cancer cells in vivo and in vitro. CONCLUSIONS: Both hsa_circ 0124055 and hsa_circ 0101622 could facilitate the prognosis and diagnosis of thyroid cancer, and function as the therapeutic targets for clinical practice.