Colorectal cancer (CRC) is the third-most common cancer around the world, accounting for approximately 10% of cancer-related mortality. Deeper molecular understanding of colorectal carcinogenesis will provide evidences for identification of early diagnostic indicators and novel therapeutic strategies for CRC treatment. The p21cdc42/rac1 -activated kinase 5 (PAK5) has been reported to be involved in a variety of tumor-promoting behaviors, whereas the underlying mechanisms of PAK5 in CRC progression are still obscure. Our current study revealed an upregulated expression of PAK5 in human CRC tissues as compared with normal adjacent biopsies, which was associated with tumor progression and metastasis. We further unraveled that inhibition of PAK5 was correlated with restrained proliferation, migration, and invasion of CRC cells in vitro and in vivo. Moreover, we showed an indispensable role of PAK5 in interacting with Cdc42 and Integrin