Background and Aims Resveratrol has a broad spectrum of anti-tumor effects, exhibiting the ability to inhibit proliferation and migration of papillary thyroid cancer cells. However, the underlying mechanisms of its actions remain unclear. This study was conducted to investigate the inhibitory effect of resveratrol on transplanted tumors of papillary thyroid cancer cells and its action mechanism.Methods Forty nude mice were subcutaneously inoculated with thyroid cancer cells (TPC-1) to establish the xenograft models. Then, the tumor-bearing mice were randomly divided into a model control group and three resveratrol treatment groups receiving different doses of resveratrol (2.5, 5, 10 mg/kg), with each group containing 10 mice. Respective doses of resveratrol were administered by intraperitoneal injection to the mice in the treatment groups, while the model control group received an equivalent volume of physiological saline, once daily for 21 d. Tumor growth was monitored and growth curves were plotted. After 21 d, mice in each group were euthanized, tumors were weighed, and tumor inhibition rates were calculated. Histological examination with HE staining and TUNEL staining were performed to assess tumor cell morphology and apoptosis. qRT-PCR and Western blot analyses were used to evaluate the mRNA and protein expressions of apoptosis-related proteins (caspase-3, Bax, Bcl-2) and epithelial-mesenchymal transition (EMT) related molecules (E-cadherin, N-cadherin, vimentin) in tumor tissues.Results In all three resveratrol treatment groups compared to the model control group, the growth rates of transplanted tumors were significantly inhibited, and after 21 d, tumor mass was noticeably reduced, and tumor inhibition rates increased with higher resveratrol doses (all P<0.05). Results of HE staining showed that in the model control group, cancer cells in the tumor tissue presented a patchy distribution with varied morphologies and sizes, rich cytoplasm, large nuclei, visible mitotic figures, and disrupted polarity. In contrast, in the resveratrol treatment groups with three different doses, there was a varying degree of reduction in cell numbers, loosening of cell arrangement, condensed cell nuclei, fewer mitotic figures, and varying degrees of focal necrosis. Compared to the model control group, the tumor tissues in the resveratrol treatment groups exhibited an increase in apoptosis of tumor cells, and showed increased expression of E-cadherin and Bax mRNA and protein, decreased expression of N-cadherin, vimentin, and Bcl-2 mRNA and protein; caspase-3 mRNA levels decreased, while cleaved caspase-3 protein expression increased. Moreover, these changes exhibited a dose-dependent relationship in all three resveratrol treatment groups (all P<0.05).Conclusion Resveratrol promotes apoptosis of papillary thyroid carcinoma cells, thereby inhibiting their growth in mice. The mechanism of action may involve the revercal of the EMT process.