Colorectal cancer is one of the most common alimentary malignancies. Slug has been shown to be an ideal target for cancer gene therapy by numerous studies due to its strong anti‑apoptotic effect. The elevated expression of Slug is a frequent genetic abnormality observed in colorectal cancer. In the present study, a Slug short hairpin RNA (shRNA) expression vector that was able to efficiently inhibit the expression of Slug in HCT116 cells was prepared. Following transfection, the mRNA expression levels were detected by RT‑PCR analysis. Western blotting detected a similar inhibition of the Slug protein levels in the cells transfected with the pGCsi‑Slug plasmid. Downregulation of Slug resulted in a significant inhibition of cancer cell growth in vitro. Cell invasion and apoptosis were decreased concomitantly with the reduction in Slug protein expression. These results suggested that RNA interference (RNAi) was able to downregulate the Slug protein level in HCT116 cells and significantly inhibit tumor growth in vitro. These findings suggest that RNAi has therapeutic potential for the treatment of colorectal cancer, as well as other types of cancer, by targeting the overexpression of oncogenes, including Slug.