Abstract Melatonin, a hormone produced by the pineal gland, is typically known for its modulation of a number of physiological functions, alongside its ability to synchronize the sleep-wake rhythms. In recent years, however, its interactions with cancerous cells and role in prevention and treatment have been increasingly studied. It has been demonstrated that melatonin can improve the efficacy of chemotherapeutic drugs and directly inhibit tumorigenesis in experimental models of neoplasia. In addition, while melatonin typically displays anti-apoptotic effects in normal cells, it holds pro-apoptotic effects in cancer cells. Despite this, the mechanisms by which melatonin affects cell death and metabolism remain unclear due to the seeming difference from cell to cell. We aim to better understand the role of melatonin in regulating thyroid cancer cell apoptosis and metabolism. The MDA-T41 thyroid cancer cell line was cultured with varying quantities of melatonin. Steady volumes of staurosporine (an inductor of apoptotic cell death) were applied to cultures, and cell death levels were subsequently measured using the Realtime-Glo Annexin V Apoptosis and Necrosis assay. Our results showed that melatonin provided anti-apoptotic effects to MDA-T41 cells treated with staurosporine. Both apoptosis and necrosis were reduced by 50% in melatonin-treated cells 24 hours after staurosporine-induced cell death. Our next steps will be to evaluate the mechanisms and further signaling pathways involved in this apoptosis inhibition through Bcl-2 and p53 protein expression. Citation Format: Angela Huang, Daniel Sanches. Evaluating the role of melatonin in thyroid cancer cell (MDA-T41) apoptosis and metabolism modulation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4853.