BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with a 20% recurrence rate. Bitter taste receptors (T2Rs) and their genes (TAS2Rs) may regulate survival in solid tumors. This study examined T2R expression and function in PTC cells. METHODS: Three PTC cell lines (MDA-T32, MDA-T68, and MDA-T85) were analyzed for expression using RT-qPCR and immunofluorescence. Live cell imaging measured calcium responses to six bitter agonists. Viability and apoptosis effects were assessed using crystal violet and caspase 3/7 activation assays. Genome analysis of survival was conducted. RESULTS: TAS2R14 was consistently highly expressed in all cell lines. Five bitter agonists produced significant cytoplasmic and mitochondrial calcium responses across all cell lines. All bitter agonists significantly decreased viability and induced apoptosis. Higher TAS2R14 expression correlated with better progression-free survival in patients (p < 0.05). CONCLUSIONS: T2R activation by bitter agonists induces apoptosis, and higher TAS2R expression is associated with survival, suggesting potential therapeutic relevance in thyroid cancer management.