Forkhead box R2 (FOXR2), a member of the FOX gene family, has not been very well investigated for its role in cancer. A recent study has shown that FOXR2 is highly expressed in breast cancer samples and is associated with poor prognosis. In addition, FOXR2 was identified as an oncogene in medulloblastoma. Nevertheless, whether FOXR2 plays a role in colorectal cancer (CRC) remains unclear. In the present study, we conducted several in vitro and in vivo studies to investigate the expression and effect of FOXR2 in CRC. The study results demonstrated that FOXR2 was upregulated in CRC tissues and cells. Downregulation of FOXR2 inhibited CRC cell proliferation, invasion, and the epithelial-mesenchymal transition (EMT) phenotype in vitro and also suppressed CRC cell growth and metastasis in vivo. Furthermore, downregulation of FOXR2 remarkably reduced the protein expression of Shh, Gli1, and Ptch1 in SW480 cells. Taken together, our data suggested that FOXR2 significantly promoted proliferation, invasion, and EMT of CRC cells. All these findings provided evidence for the role of FOXR2 as an oncogene in CRC development.