Thyroid cancer is the most common endocrine malignancy, and its incidence has increased rapidly worldwide. The molecular mechanisms underlying thyroid cancer tumorigenesis still need to be further investigated. MicroRNAs (miRNAs), short RNA molecules of approximately 22 nucleotides in length, play crucial roles in tumorigenesis. In the present study, we found that the expression of miR-144 was significantly down-regulated in thyroid cancer as compared with that in normal thyroid tissues, suggesting that miR-144 may be involved in thyroid cancer tumorigenesis. Moreover, our results showed that restoration of miR-144 in K1 and WRO thyroid cancer cells could suppress the invasion and migration capability of these cells. We also demonstrated that miR-144 suppressed the expression of ZEB1 and ZEB2, two E-cadherin suppressors, by directly binding to their 3'-untranslated regions. Furthermore, restoration of ZEB1 or ZEB2 partially rescued the miR-144-induced inhibition of cell invasion. These data suggest miR-144 function as a tumor suppressor in thyroid cancer.