Ubiquitin-proteasome system regulates cell proliferation, apoptosis, angiogenesis and motility, which are processes with particular importance for carcinogenesis.UBA protein 2-like protein (UBAP2L) was found to be associated with proteasome; however, its biological function is largely unknown.In this study, the mRNA levels of UBAP2L in human normal and colorectal carcinoma tissues were analyzed using the datasets from thepublicly available Oncomine database (www.oncomine.org).Furthermore, we elucidated the role of UBAP2L in human colorectal cancer via an RNA interference lentivirus system in two colorectal carcinoma cell lines HCT116 and SW1116.Knockdown of UBAP2L led to suppressed cell proliferation and impaired colony formation.UBAP2L depletion in HCT116 cells also induced cell cycle arrest as well as apoptosis.Moreover, the activation of P38was obviously decreased, and the phosphorylations of PRAS40, Bad and the cleavage of PARP were remarkably increased after UBAP2L knockdown, indicating such signaling pathways might be involved in the cell growth regulation by UBAP2L.Our findings indicated that UBAP2L was essential for colorectal carcinoma growth and survial.Lentivirus-mediated small interfering RNA against UBAP2L might serve as a potential therapeutic approach for the treatment of colorectal cancer.