Background: Leukemia is a hematological malignancy characterized by the proliferation of early lymphoid precursors that replaces normal hematopoietic cells of the bone marrow. Nakhi (Naxi) ethnic minorities considered to be an area of low incidence. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the expression of other genes in various biological processes. The purpose of this work is to study the molecular mechanism of miRNAs in the leukemia from Naxi. Methods: Six leukemia patients (case 2 to case 7) and one healthy person (case 1) from Nakhi (Naxi) ethnic minorities were recruited. Total RNA was extracted from these samples and small RNA deep sequencing was performed. Results: A list of miRNAs (1,392 known and candidate 125 novels) expressed in leukocytes were identified, and many differentially regulated targets involved in several cellular pathways, such as cancer, Rap1 signaling pathway, Ras signaling pathway, and endocytosis. Additionally, quantitative real time-polymerase chain reaction (qRT-PCR) results show that hsa-miR-181b-5p, hsa-miR-181a-3p, hsa-miR-181a-5p, and hsa-miR-342- 3p has different expression patterns in different cancer cells, hsa-miR-450a-5p, and hsa-miR-1255a were dysregulated in all leukemia cells. Conclusions: Several abnormal expressed miRNAs in leukemia patients were identified, the correlation of miRNAs dysregulation and leukemia biology demonstrates that specific miRNA can be potential therapeutic target.