BACKGROUND WD40-encoding RNA antisense to p53 (Wrap53) has been implicated in cancer development. However, the role of Wrap53 remains unknown in colorectal cancer. The aim of this study was to elucidate the function of Wrap53 in colorectal cancer tumorigenesis and development. MATERIAL AND METHODS This study analyzed Wrap53 expression in colorectal cancer tissue specimens using The Cancer Genome Atlas data and tumor cell lines and assessed the effects of Wrap53 knockdown on regulation of cancer cell malignant phenotypes in vitro and in nude mouse xenografts. RESULTS Wrap53 expression was upregulated in colorectal cancer tissue specimens and cell lines. Knockdown of Wrap53 expression induced colorectal cancer cell line apoptosis and cell cycle arrest in the G1 phase, but reduced tumor cell line proliferation and invasion in vitro. Knockdown of Wrap53 in a nude mouse xenograft assay inhibited tumor cell line xenograft formation and growth. CONCLUSIONS Wrap53 is likely a potential oncogene or possesses oncogenic activity in colorectal cancer, promoting colorectal tumorigenesis. Targeting Wrap53 expression may represent a novel strategy for the control of colorectal cancer.