miR-142 and miR-223 have been identified as hematopoietic specific microRNAs. miR-223 has crucial functions in myeloid lineage development. However, the function of miR-142 remains unclear. In this study, we found that both miR-142 and miR-223 attenuated the proliferation of hematopoietic cells, and that miR-223 up-regulated miR-142 expression through the LMO2-L/-S isoforms and CEBP-β. miR-223 negatively regulated both LMO2-L/-S isoforms and CEBP-β post-transcriptionally, while CEBP-β positively regulated the LMO2-L/-S isoforms and both of the LMO2-L/-S isoforms negatively regulated miR-142. These results reveal a novel miR-223—CEBP-β—LMO2—miR-142 regulatory pathway, which has pivotal functions in hematopoiesis.