Although human T cell leukemia virus type I (HTLV-I) is undoubtedly involved in the immortalization and leukemogenesis of infected cells, mechanistic underpinnings of its molecular pathophysiology in long latent period of Adult T-cell leukemia (ATL) remain to be elucidated. One of the most significant recent advances in biomedical research has been the discovery of small noncoding RNAs designated microRNA (miRNA), which affect the field of virology including HTLV-1 research. Mounting evidence indicates that viruses use these miRNAs to manipulate both cellular and viral gene expression. Viral infection also can exert a profound impact on the cellular miRNA expression profile. Some studies have demonstrated that some deregulations of miRNA are involved in the pathogenesis of HTLV-1. Furthermore, global analyses of ATL patient samples have provided a conceptual progress that Polycomb family induces miR-31 silencing, resulting in overexpression of NF- kappaB inducing kinase (NIK) following NF-kappaB activation. Given that miRNAs act as pleiotropic molecules essential in all cellular events, deregulation of miRNA signature caused by HTLV-1 infection strongly involves the imbalance of molecular network of lymphocytes. Recognition and understanding of the widespread molecular applicability of miRNAs will increasingly have much effect on the development of novel strategies to treat the HTLV-1-associated diseases. Here we discuss our current knowledge of viral miRNAs and virally influenced cellular miRNAs and their relationship to ATL.