Dysregulation of microRNAs (miRs) has been linked to several types of cancer. In the present study, we investigated the expression of miR-181a in different leukemia cell lines and healthy hematopoietic cells, as well as its influence on cell proliferation, metabolic activity and potential targets. Expression of miR-181a differed between various leukemia cell lines and mature blood cells. Inhibition of miR 181a expression in T- and B-Acute Lymphoblastic Leukemia (ALL) cells revealed an influence on the potential targets High-Mobility-Group-Protein B1 (HMGB1) and Cluster of Differentiation 4 (CD4). Overexpression of miR-181a in AML cells led to a significant decrease in cell proliferation and metabolic activity. The present data indicate a possible role of this specific miRNA in immunogenicity.