© 2021 A. CARBONE Editore. All rights reserved.Introduction: This study aimed to demonstrate expression changes of Notch1, Notch4, Jagged1, leptin, leptin receptor ObRb, interleukin-1a (IL-1a), IL-1β, IL1R, Vasoactive Growth Factor-A (VEGFA), VEGFR1, VEGFR2, IL-6 genes in human thyroid cancer tissues. Also, leptin, T3, and T4 concentrations in plasma of both thyroid cancer and healthy controls were compared. Materials and methods: Notch1, Notch4, Jagged1, leptin, leptin receptor ObRb, IL-1α, IL-1β, IL1R, IL-6, VEGFA, VEGFR1, and VEGFR2 mRNA expressions were analyzed by qRT-PCR in human tissue of normal and thyroid tumors from 27 patients. The plasma leptin, T3, and T4 concentrations were determined was by ELISA. Results: In this study, we showed that Notch4, Jagged1, leptin, IL-1α, IL1R, VEGFA, VEGFR2, and IL-6 are over-expressed in human thyroid carcinoma tissues compared with normal thyroid tissues. Also, mean plasma leptin, T3, and T4 concentration were significantly higher in thyroid cancer patients compared with healthy controls. The activation of Notch4 and Jaggedl is associated with leptin, IL-1α, and IL1R mRNA expressions, and this positive correlation can also be attributed to clinicopathological parameters. Moreover, we have shown that plasma concentration levels of leptin, T3, and T4 are related and contribute to poor survival results. Conclusion: These results indicate that NILCO (Notch, IL-1 and Leptin) could be critical in the development of thyroid cancer and this is a useful clinical biomarker in thyroid carcinoma.