<p>The bat-borne Nipah virus, known for causing high mortality rates in humans, has been reported in India (<i>Megaderma spasma</i>), Bangladesh (<i>Pteropus medius</i>), and Malaysia (<i>Pteropus vampyrus</i>) with different bat species serving as reservoirs. The virus also infects various animals, which often act as intermediate hosts in the transmission to humans. Due to the high fatality rates associated with Nipah virus outbreaks, the World Health Organization has flagged it as a significant public health concern, prompting extensive research into the development of antiviral therapeutics and vaccines. However, no effective vaccine or therapeutic agent has yet been established. In this context, we propose a miRNA-based approach to identify key human cellular miRNAs capable of binding to and potentially cleaving or degrading Nipah virus genes implicated in human infections. Our study revealed a substantial number of miRNA binding sites across various viral genes, suggesting a potential mechanism for gene silencing. Furthermore, the calculated free energy values (&lt; 4&#xa0;kcal/mol) for all three regions; downstream, upstream and target indicate that the thermodynamically favorable binding could facilitate effective miRNA-mediated repressions of viral gene expression. Additionally, the translational efficiency and COSM values suggested swift miRNA-mediated cleavage or degradation of the viral genes. Moreover, analysis of the miRNA-mRNA duplex free energy and secondary structures, as predicted by RNAFold, indicated that the interactions between human miRNAs and Nipah virus genes were thermodynamically stable. These stable duplex formations support the potential for efficient binding, leading to effective gene silencing through cleavage or degradation mechanisms.</p>