MicroRNAs (miRNAs) are known to be critical regulators in cancer progression. MiR-451a is reported to be involved in the progression of many different forms of cancers, including osteosarcoma, colorectal cancer, and breast carcinoma. In this study, we illuminated the possible roles of miR-451a in the development of papillary thyroid carcinoma (PTC) cells in vitro and in vivo. MiR-451a was markedly down-expressed in PTC sample compared with paratumor tissue. Upregulation of miR-451a repressed PTC cells proliferation, migration ability and inhibited the invasiveness of PTC cells in vitro. Additional, miR-451a suppressed PTC cells growth and the lung metastasis of PTC cells in vivo, whereas downregulation of miR-451a caused opposite outcomes. Importantly, miR-451a inversely modulated the expression of Zinc Finger E-Box Binding Homeobox 1 (ZEB1) by directly binding to the 3′ untranslated region (UTR) of ZEB1 in PTC cells. The level of ZEB1 was negatively associated with miR-451a level in PTC tissues, and ZEB1 silencing mimicked the suppressive impacts of miR-451a on the proliferation, mobility, and invasive phenotypes of PTC cells. ZEB1 overexpression abrogated the inhibitory impacts of miR-451a on PTC cells. Together, this study revealed that miR-451a restrained the growth and metastatic phenotypes of PTC cells through targeting ZEB1.