Colorectal cancer (CRC) is one of the most prevalent malignant tumors with limited treatment options. Therefore, there is an urgent need to investigate new therapeutic targets against CRC. Ubiquitous Kruppel-like factor (UKLF) is involved in various cancer processes, but its effect and detailed molecular mechanism in CRC are not yet fully understood. Here, this study aimed to investigate the function and mechanism of UKLF in the development of CRC. The results showed that UKLF was highly expressed in CRC tissues from clinical patients and its high expression was related to poor prognosis. UKLF promoted cell proliferation, migration and invasion, and inhibited cell apoptosis. The promotion effect of UKLF on tumor growth was further confirmed in vivo. As far as the mechanism was concerned, poly (C) binding protein 2 (PCBP2) was verified to bind to the 3'-UTR of UKLF mRNA and enhance its mRNA stability. Moreover, UKLF modulated the expression of solute carrier family 39 member 4 (SLC39A4) at the transcriptional level. Taken together, these findings elucidated the regulatory mechanism of UKLF and uncovered the importance of the PCBP2/UKLF/SLC39A4 pathway. The targeting of UKLF may be a novel direction for molecular-targeted CRC therapy.