Background: Interferon Regulatory Factor-2 Binding Protein-2 (IRF2BP2) is a member of IRF2BP family of proteins, which were initially identified as transcriptional corepressors that were dependent on IRF-2. IRF-2 transcription factor is known for controlling the expression of interferon (IFN)-responsive genes, which in turn act in the regulation of the cell cycle and/or apoptosis. Although the actual involvement of IRF2BP2 genes transcription has not yet been demonstrated and its physiological role is still poorly understood, recent data suggest the participation of IRF2BP2 in cell cycle regulation, cell death, angiogenesis, immune response and inflammation. These findings indicate that an imbalance in IRF2BP2 function could be related to cancer development. Objectives and Methods: The main objective of this study is to investigate the role of IRF2BP2 in cell cycle control and cell transformation, and thus to determine the relevance of this protein in tumorigenesis. To investigate the role of IFR2BP2 in cell cycle regulation, NIH3T3 murine fibroblast cells were transduced with retroviral vector containing the Irf2bp2 gene under the control of a tetracycline-responsive promoter. Cell proliferation, cell cycle progression, cell death and cell transformation were evaluated by flow cytometry, in vitro clonogenic assays and focus formation, and in vivo tumor formation in nude mice. In addition, gene expression profiles were analyzed by transcriptome by RNA-seq carried out from transduced NIH3T3 cells samples. Results: Overexpression of Irf2bp2 lead a decreased cell proliferation due to a delay in S-phase entry. Additionally, overexpression of Irf2bp2 in cells transformed with H-ras-V12 diminished the formation of culture foci, semi-solid colonies and mouse tumors. RNA-seq evaluation demonstrated an enriched several cellular pathways important in the carcinogenesis process in cells overexpressing IRF2BP2, such as the cell cycle pathway, hypoxia, angiogenesis, and pathways related to immune response. Conclusions and Implications: Our data showed that IRF2BP2 act as inhibitor of tumor development, inducing lower proliferative potential through repressing the expression of cell cycle genes in NIH3T3 cells. Finally, these data suggest that IRF2BP2 may act as a tumor suppressor gene and could be a potential biomarker for tumor development.