Follicular thyroid carcinoma (FTC) is a common endocrine malignancy with highly aggressive features. In this study, next-generation sequencing technology was used to identify aberrant expression of sialyltransferase (ST) family members in FTC. Aberrant high expression of alpha-2,6-sialyltransferase 2 (ST6GAL2) was demonstrated to promote tumorigenesis of FTC in vitro and in vivo. Furthermore, ST6GAL2 promoted tumorigenesis by inactivating the Hippo signaling pathway. Resveratrol is a native compound extracted from Vitis species, and many studies have confirmed its protective cardiovascular and antineoplastic effects. Here we found that resveratrol can inhibit the tumorigenesis of FTC by suppressing the expression of ST6GAL2, further activating the Hippo pathway. In summary, this study revealed the role of the ST6GAL2-Hippo signaling pathway in FTC tumorigenesis and indicated that resveratrol, a commonly found antineoplastic compound, could inhibit tumorigenesis of FTC by regulating the abovementioned pathways.Recently, sialyltransferase (ST) families have been reported to be critical cancer-regulating factors. 10 Sialylation is a key process in eukaryotic cells that has been shown to act in cell recognition, cell adhesion, receptor activation, and protein stability. 11 Therefore, STs contribute greatly to tumor development by acting as catalysts of sialylation. STs are categorized into four families: ST3GAL, ST6GAL, ST6GALNAC, and ST8SIA. 12 As reported, ST6GAL1 and ST3GAL6 regulate tumorigenesis of human colorectal carcinoma, 13,14 ST6GALNAC2 regulates breast cancer invasion, 15 and ST8SIA2 regulates cell invasion of non-small cell lung cancer. 16 Moreover, similar findings were reported in our previous study, which showed that alpha-2,6-sialyltransferase 2 (ST6GAL2) is highly expressed in FTC and regulated by the long noncoding RNA-HLA complex P5 (HCP5). 17 However, the downstream regulatory mechanisms of ST6GAL2 in FTC are not clear.