Dengue virus nonstructural protein 1 (NS1) is a glycoprotein involved in viral RNA replication. NS1 associates with host cell proteins and can be found in lipid raft domains on the host cell surface, suggesting an involvement in signal transduction events. In this work, we observed that NS1 expression in HepG2 cells increases nuclear translocation of NF-κB p65 protein, which was paralleled by DNA-protein complex formation. Luciferase assays showed an increase in NF-κB transcriptional activities in NS1-expressing cells when compared to parental cells. NS1 may enhance NF-κB function in host cells and contribute to the pathogenesis of dengue.