The present study was to examine the effect of Tripartite motif 16 (TRIM16) on epithelial mesenchymal transition (EMT) and metastasis in non-small cell lung cancer (NSCLC) cells, and its clinical significance in NSCLC. The correlation of TRIM16 expression and clinical features of NSCLC was analyzed in paraffin-embedded archived normal lung tissues and NSCLC tissues by immunohistochemical analysis. The effect of TRIM16 on EMT and metastasis was examined both in vitro and in vivo. The expression of TRIM16 was markedly decreased in NSCLC and correlated with tumor metastasis. Upregulation of TRIM16 significantly inhibited EMT and metastasis of NSCLC cells. In contrast, silencing TRIM16 expression significantly promoted the EMT and metastasis of NSCLC cells both in vitro and in vivo. Moreover, we demonstrated that downregulation of TRIM16 activated the sonic hedgehog pathway, and that inhibition of the sonic hedgehog pathway by cyclopamine abrogated the effect of TRIM16-downregulation induced EMT and metastasis on NSCLC cells. Our results suggest that TRIM16 is a potential pharmacologic target for the treatment of NSCLC and promotion TRIM16 expression might represent a novel strategy to NSCLC metastasis. (C) 2015 Elsevier Inc. All rights reserved.