Thyroid cancer is the most important malignant tumor reported in human populations where, its treatment remains undeveloped. Fisetin, a plant flavonoid exhibits several pharmacological properties like antioxidant, anti-inflammatory, and anticancer function. In the existing study, we assessed fisetin mediated cytotoxic effects and action potential of fisetin on cell proliferation in TPC-1 human cancer cells. Also, examined the apoptosis in TPC-1 cells by reactive oxygen species (ROS) generation, the mitochondrial membrane potential (MMP) and apoptotic morphological changes through AO/EtBr staining. Additionally, we analyzed the effects of fisetin through ELISA analysis to evaluate the caspases expression and studied JAK 1 and STAT3 signaling molecule in TPC1 cells. Our results demonstrated that fisetin stimulated apoptosis, which confirmed through reduced cell viability, improved ROS generation, altered MMP and cell cycle phases in TPC-1 cells. Further, the fisetin up-regulated the expression of caspase (3, 8, and 9) expressions in TPC-1 cells. Also, we observed the fisetin down-regulated the JAK 1 and STAT3 expression in TPC1 cells. Thus, the fisetin induced apoptosis in TPC-1 cells by the induction of oxidative damage and enhanced caspases expression by down-regulating JAK 1 and STAT3 signaling molecules. Hence, the fisetin would be considered as a beneficial therapeutic agent for the thyroid cancer treatment.