NPCEDRG is an NPC associated suppressive gene cloned by positional candidate cloning strategy. Its transcriptional down-expression has been shown in the cell lines and primary tumor tissues of NPC. Reintroduction of NPCEDRG into CNE2, a cell line derived from NPC, was effective to induce cell differentiation, control cell growth, and regulate the cell cycle. To uncover the molecular mechanisms underlying down-expression of NPCEDRG in NPC cells, bioinformatics approaches and functional assays in different tumor cell lines were used to identify and characterize the NPCEDRG core promoter and cis-acting elements. The conserved region from -180 to +235 bp was found in the potential promoter among 6 vertebrate species by the ECR browser, and there have several potential binding sites for transcription factors, such as CCAAT/NFY, STAT1 and SP1. To characterize the NPCEDRG core promoter, transient luciferase and/or EGFP reporter assay were carried out with the construct pGL3-en138. The results demonstrated that the core promoter is located at the conserved region from -146 to -8 nucleotides. Gel shift assay revealed the specific binding of some nuclear proteins to probes containing a putative CCAAT/NFY site，suggesting that the CCAAT/NFY site contributes to the regulation of NPCEDRG gene expression.