Targeted inhibition of cyclin-dependent kinase 7 (CDK7) via its covalent inhibitor THZ1 can suppress the growth of various cancers, while its roles on colorectal cancer (CRC) remain obscure. Here we report that the expression of CDK7 is upregulated in CRC cells and tissues. THZ1 exhibits high potency and selectivity against CRC cells both in vitro and in vivo via induction of cell apoptosis rather than cell cycle disruption. Intriguingly, THZ1 treatment increases the ability of epithelial mesenchymal transition (EMT) and in vivo metastasis to liver of CRC cells. Mechanistical studies reveal that THZ1 increases the expression of Snail, while not other EMT-transcription factors, via enhancing its protein stability rather than mRNA expression or translation. By screening Snail stability related factors via qRT-PCR, results indicate THZ1 and si-CDK7 decrease the expression of protein kinase D1 (PKD1) in CRC cells. Down regulation of PKD1 mediates THZ1 up regulated Snail via dephosphorylation of Snail Ser 11 and prevention of proteasome mediated degradation. Clinical analysis confirms that CDK7 is significantly (p