Dengue virus (DENV) infection is the most widespread viral disease transmitted by insect vectors worldwide. Mild and severe clinical dengue disease processes can occur after human infection. DENV escapes recognition and attack by the immune system, mainly by resisting transduction of the human interferon (IFN) signaling. Moreover, mice are naturally resistant to DENV infection. Therefore, researchers have been attempting to induce DENV infection by establishing a mouse model devoid of IFN signaling pathway-related molecules. However, it remains difficult to accurately replicate the clinical characteristics of DENV infection. This review summarizes the immune escape mechanism of dengue virus by IFN signaling pathways. This article also analyzes the applications of the mouse model devoid of such pathways to uncover the pathogenic mechanisms of dengue virus and develop effective vaccines and drugs. In conclusion , we in propose that a better mouse model that closely simulates the processes of different diseases after clinical DENV infection may be established by modifying the present models in humans.