Introduction: MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate transcriptional and posttranscriptional gene regulation of the organisms. miRNA provides immune defense when the body is faced with challenges intracellular agents. miRNA molecules trigger gene silencing in eukaryotic cells. More than 3,000 different human miRNAs (hsa-miRs) have been identified thus far. During ontogenesis, viral or intracellular parasitic infections, miRNAs are differentially expressed to protect the host from intracellular invaders. In a viral infection context, miRNAs have been connected with the interplay between host and pathogen, and occupy a major role in pathogenesis. Methodology: An in silico approach was used to analyze the four major Ebola Virus genome sequences including the recently characterized Ebola virus responsible for West African epidemic that has killed over 10,000 people. All totaled, 2,543 mature human miRNA sequences were retrieved through an miR-database, and the identification of mature miRNAs were aligned with full length sequences of the four major Ebola viruses via computational tools. Results: We identified 32 miRNAs that exhibited significant inhibitory capacity to block more than one EBV strains. miR-607 showed capacity to quell all four major EBVs. Ten putative miRNAs were found to have near perfect identity at seed sequences with numerous targets of Ebola virus that may completely degrade the viral transcripts. Conclusion: We hypothesize that a miRNA-based vaccine can quell Ebola virus infection. Future approaches will focus on validation of these miRNAs in quelling the Ebola virus to further elucidate their biological functions in primate and other animal models.