Colorectal cancer (CRC) is a major cause of cancer mortality worldwide, however, the molecular mechanisms underlying the pathogenesis of CRC remain largely unclear. Recent studies have revealed crucial roles of transcription factors in CRC development. Transcription factors essential for the regulation of gene expression by interacting with transcription corepressor/enhancer complexes and they orchestrate downstream signal transduction. Deregulation of transcription factors is a frequent occurrence in CRC, and the accompanying drastic changes in gene expression profiles play fundamental roles in multistep process of tumorigenesis, from cellular transformation, disease progression to metastatic disease. Herein, we summarized current and emerging key transcription factors that participate in CRC tumorigenesis, and highlighted their oncogenic or tumor suppressive functions. Moreover, we presented critical transcription factors of CRC, emphasized the major molecular mechanisms underlying their effect on signal cascades associated with tumorigenesis, and summarized of their potential as molecular biomarkers for CRC prognosis therapeutic response, as well as drug targets for CRC treatment. A better understanding of transcription factors involved in the development of CRC will provide new insights into the pathological mechanisms and reveal novel prognostic biomarkers and therapeutic strategies for CRC.