MicroRNA-145 (miR-145) has been implicated in several cancers. However, its role in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we proved that miR-145 was significantly downregulated in NPC and associated with NPC cell metastasis. Moreover, miR-145 suppressed Smad3 by directly binding to the 3'-untranslated region (UTR) of Smad3. Knockdown of Smad3 in NPC cells inhibited cell migration and invasion, which was consistent with the effect of miR-145 in NPC cells. In addition, Smad3 expression was inversely correlated with miR-145 level in clinical NPC samples. Taken together, our findings indicate that miR-145 is a tumour suppressor that affects invasive and metastatic properties of NPC via the miR-145/Smad3 axis, leading us to propose that miR-145 overexpression might be a potential therapeutic strategy of NPC intervention.