In this study, we demonstrated that ubiquitin C-terminal hydrolase L1 (UCHL1) is upregulated in non-small cell lung cancer (NSCLC) and drives tumor metastatic progression, and we identified Twist1, a transcription factor that governs epithelial-mesenchymal transition (EMT), as a downstream target of UCHL1. This evidence concerns the gene TWIST1 and neoplasm.