Objective：To investigate the global miRNA expression profiles and chromosome distribution characteristics in peripheral blood mononuclear cells（PBMC） of children with Down syndrome（DS） and without DS. Methods：Illumina deep sequencing technol－ogy was used to analyze the global miRNA expression profiles and chromosome distribution in 6 pairs of PBMC samples from DS children（DS group） and non-DS children（control group）. Stem-loop qRT-PCR was employed to verify the results of Illumina deep sequencing technology. Results：There were 911 miRNAs expressed that were encoded by 738 miRNA genes，which had the same chromosome distribution in both groups. However，the expressive abundance of chromosome distribution was different：DS group was mainly scattered in 7，13 and 21 chromosomes，while the control group was majorly scattered in 7 and 13 chromosomes. Furthermore，114 of 911 miRNAs were significantly differentially expressed in both groups（difference multiple≥2，P<0.001）. In the DS group，11 miRNAs were low expression and 103 miRNAs were high expression，including 5 miRNAs encoded by 21 chromosome（miR-99a，let-7c，miR-125b，miR-155，miR-802）. Conclusion：PBMCs of DS children have specific miRNA expression profiles and chromosome distribution characteristics. Differences of expressive abundance of miRNAs encoded by the chromosome may be associated with clin－ical symptoms in DS patients，such as immune deficiency.