The importance of membraneless organelles and these formation mechanisms, liquid-liquid phase separation (LLPS) has recently gained large attention due to new understandings on their roles in cellular functions including transcription, RNA splicing and signal transduction. Paraspeckles are well-known membraneless organelless located in the interchromatin space of mammalian cell nuclei and consist of multiple proteins and RNAs, including NONO, SFPQ and NEAT1. These paraspeckle components are highly expressed in hematopoietic cells. However, their roles in hematopoiesis are largely unknown. In this study, we found an unexpected involvement of epigenetic regulator ASXL1 in paraspeckle formation in hematopoietic cells. ASXL1 has a long intrinsically disordered region (IDR) in its C-terminal region and forms phase-separated droplets in vitro. Of note, a large part of the IDR is located behind the mutational hotspot of ASXL1 gene, suggesting that most pathogenic ASXL1mutants lack IDR. Interestingly, the mutant ASXL1 (ASXL1-MT) lacking its C-terminal IDR could not form droplets efficiently. ASXL1 upregulates NEAT1 expression and increases NONO-NEAT1 interaction, while a pathogenic ASXL1-MT does not support the interaction among paraspeckle components. Consequently, we observed disruption of paraspeckles and aberrant localization of Nono in cytoplasm of hematopoietic stem and progenitor cells (HSPCs) derived from ASXL1-MT knockin mice. We also showed that NONO depletion and forced expression of cytoplasmic NONO impair repopulating potential of HSPCs as ASXL1-MT does. The present findings highlight the potentially important role of paraspeckles in hematopoiesis and hematopoietic disorders.