Luciferase reporter gene assays and immunofluorescence staining were used to investigate the effects of IRX4 overexpression on the activation of the nuclear factor-κB (NF-κB) pathway and the nuclear translocation of the p65 subunit.<h4>Results</h4>IRX4 was downregulated in CRC tissues and cell lines, and its expression was negatively correlated with tumor invasion depth and poor prognosis. Here, NFKB1 is linked to neoplasm.