Aim: This study was first performed to investigate the role of octamer-binding transcription factor 4 (OCT4) in colorectal cancer (CRC). Methods: The electronic databases were searched for the eligible studies. Odds ratios and hazard ratios were calculated. Functional analysis of OCT4 was examined. Results: Eight studies with 1480 CRC cases were identified. OCT4 expression was correlated with advanced clinical stage, tumor grade, lymph node metastasis, lymphatic invasion, and distal metastasis. OCT4 was an independent prognostic biomarker for predicting worse disease-specific survival and overall survival in CRC. The functional analyses demonstrated that OCT4 was involved in multiple functions, such as cell adhesion, phosphoinositide 3-kinase/Akt signaling, and regulating pluripotency of stem cells. Conclusion: OCT4 may be correlated with disease progression and metastasis, and could predict prognosis in CRC.