Although the biological functions of miR-744 and miR-484 are poorly understood, they appear to be highly conserved in vertebrates. The gene encoding miR-744 locates at chromosome 17p12 and is implicated in the cellular process leading to human disease development. The function of miR-744 depends on the cell type and it acts as either a tumour suppressor or a tumour promoter. The gene encoding miR-484 locates at chromosome 16p13 and is essential for cerebral cortex development. Both, miR-744 and miR-484 are mainly expressed in the brain, but they can also be found in the liver and blood. miR-484 was significantly differentially expressed in the serum of patients with early breast cancer versus healthy controls; however, no correlation could be established between miR-484 levels and the histopathological parameters of breast cancer (Zearo et al. 2014). miR-744 is suggested to play an inhibitory role in many cancers, including colon, breast, and gastric cancer. It was recently reported that miR-744 inhibits the growth, migration, invasion, proliferation, and metastasis of gastric cancer by targeting Bcl-2 protein expression (Chen & Liu 2016). Furthermore, a lower miR-744 expression level was reported in patients with hepatocellular carcinoma (HCC) and this was associated with HCC recurrence and prognosis (Tan et al. 2015). However, studies regarding the role, effect, and significance of miR-484 and miR-744 on viral infections are still insufficient. Therefore, the main objective of this study was to determine the role of miR-484 and miR-744 in DENV infection and to examine whether DENV infection alters the expression of both these miRNAs. While our results were obtained using Vero, a cell line highly susceptible to DENV infection, we have also observed that macrophages and dendritic cells, which are both targets of DENV infection, also express miR-484 and miR-744 (unpublished observations). Therefore, we explored the relationship between DENV and cellular miRNAs using bioinformatics tools. We then overexpressed miR-484 or miR-744 in Vero cells to test their role in DENV replication, and finally determined the effect of DENV infection and the effect of the 3′ UTR of DENV RNA on miR-484 and miR-744 expression in Vero cells. We observed that overexpression of either miR-484 or miR-744 diminishes the replication of all four DENV serotypes. Finally, infection and transfection of Vero cells with a plasmid construct encoding the 3′ UTR of DENV RNA resulted in downregulation of endogenous miR-484 and miR-744. This is one of the first studies to demonstrate the effect of two cellular miRNAs on regulating the replication of the 4 DENV serotypes. Our study thus helps us to better understand the relationship between host cells and DENV infection. Although additional studies are required to unambiguously confirm the function of miR-484 and miR-744, our preliminary data suggest that these miRNAs might play a role in DENV replication.