Previous studied revealed that miR-758-3p was abnormally expressed in cancer patients. However, its role and underlying mechanism in papillary thyroid cancer (PTC) remains unclear. Expression of miR-758-3p in PTC cell lines was analyzed using quantitative real-time PCR. It was observed that miR-758-3p expression was significantly downregulated in PTC cell lines. Overexpression of miR-758-3p inhibited PTC cell proliferation, invasion but promoted cell apoptosis in vitro. Further study demonstrated that TGF-β activated kinase 1 binding protein 1 (TAB1) was a direct target of miR-758-3p and TAB1 expression was suppressed by miR-758-3p overexpression. Moreover, TAB1 was shown to be a mediator for the roles of miR-758-3p in PTC. Therefore, our study established a tumor-suppressive role for miR-758-3p in the inhibition of PTC progression, which may be employed as a novel prognostic marker and as an effective therapeutic target for PTC.