Given its role in tumorigenesis and its correlation with various pathologic features of colorectal cancer (CRC), DEK is considered to have the potential to predict CRC prognosis. This review attempts to summarize current knowledge and evidence supporting the potential of DEK as a prognostic biomarker of CRC. We searched meta-analyses, systematic reviews, cohort studies, and cell line studies published in the last 10 years. A literature search was conducted in PubMed, Pubmed Central (PMC), Proquest, EBSCOHost, Scopus, and Cochrane Library using the keywords 'colorectal/colon/rectal cancer', 'DEK', 'biomarker', and 'prognosis'. Studies that were not published in English, without accessible full text, unrelated to clinical questions, or conducted with a design unsuitable for the eligibility criteria were excluded. Seven included studies reported the potential of DEK as a prognostic biomarker of CRC and its role in cancer cell proliferation, invasion, and metastasis. This role is achieved through the Wnt/β-catenin pathway, prevention of apoptosis through destabilization of p53, and bridging inflammation and tumorigenesis through the nuclear factor (NF)-κB pathway, causing chronic inflammation and activation of tumorigenic genes. DEK overexpression is also associated with CRC clinical and pathological features, such as tumor size, lymph node metastasis, serosal invasion, differentiation, tumor staging, and epithelial-mesenchymal transition. DEK overexpression was found to be associated with lower survival and recovery rates. Its prognostic value was comparable with other prognostic biomarkers of CRC, such as BRAF, topoisomerase-1, and CEA. A cohort study reported that DEK overexpression was associated with a better response to fluoropyrimidine-based chemotherapy, while a cell-line study indicated a correlation between DEK overexpression with a worse response to irinotecan-based chemotherapy. In conclusion, considering its correlation with CRC pathology, its association with worse CRC patient survival, and its possibility to forecast the therapeutic response of various chemotherapeutic regimens, DEK has the potential to be used as a CRC prognostic biomarker.