Mammalian Rpn13, a 26S proteasome ubiquitin receptor subunit, binds to ubiquitin substrate at the N terminal but deubiquitin enzyme UCH37 at the C terminal. Rpn13 is known to mediate degradation of most proteins via ubiquitin-proteasome, to regulate autophagy, neuron function, and germ cell development. Proteasome inhibitors are used for tumor prevention and treatment, targeting Rpn13 can overcome resistance against proteasome inhibitors. Transcriptional repression mechanism of its gene expression is unclear. Interactive analysis of gene expression profile revealed that Rpn13 gene was highly expressed in many cancer types, especially in colon cancer, lymphoma, pancreatic, rectal, gastric and thoracic cancers. The activity of the regulatory region −454~−58 bp of Rpn13 promoter was found to be high in double luciferase report assay. Binding sites of multiple transcription factors, including CTCFL (CCCTC binding factor-like), CTCF (CCCTC binding factor), NRF1 (Nuclear respiratory factor 1) and FOXO3 (Forkhead box O3), were predicted on the promoter sequence of Rpn13. We constructed expression plasmids of these transcription factors and found that they all inhibited Rpn13 promoter. By further mutating corresponding transcription factor binding sites of Rpn13 promoter, CTCFL was found to bind −63~−52 bp sequence of the Rpn13 promoter. These studies not only analyzed Rpn13 gene expression in cancer tissues, but also revealed possible transcription inhibition mechanism of Rpn13, providing useful clues for exploring mechanism of Rpn13 in tumor occurrence and development.