The transcription factor C/EBPα α (CCAAT enhancer binding protein) is a master regulator of granulopoiesis, which is frequently disrupted in acute myeloid leukemia (AML). MicroRNAs (miR) inhibit the translation of protein coding mRNAs; play a critical role in granulopoiesis and AML. In this study, miR-30c has been identified as a new target of C/EBPα during early granulopoiesis. The Wildtyp C/EBPα-p42 regulates the expression of miR-30c directly, whereas the short form C/EBPα-p30 has no effect on miR-30c. In AML, the expression of miR-30c is reduced. A deregulated function or block of C/EBPα leads to significant repression of miR-30c expression. Furthermore, NOTCH1 could be identified as a new functional target of miR-30c. A block of miR-30c prevents C/EBPα-induced translation of Notch1 and leads to a delay in myeloid differentiation.