〔Abstract〕 Objective To investigate the expression, clinical significance, progression, and prognosis of miR-381-3p in acute myeloid leukemia(AML), as well as its impact on AML cell proliferation and apoptosis, in order to provide theoretical basis for the treatment of AML. Methods Bioinformatics analysis was used to identify differentially expressed miRNAs, clinical data and blood samples of AML patients were collected, and the expression levels of miRNAs in the bone marrow fluid of the included patients were measured to further elucidate the relationship between miRNAs and AML. The included patients were followed up to calculate overall survival(OS) and disease-free survival(DFS); AML cells were culturedin vitro, miR-381-3p plasmids were constructed, miR-381-3p was overexpressed and miR-381-3p was knocked down in AML, and they were divided into five groups: control, miR-381 mimics, mimics NC, miR-381 inhibitor, inhibitor NC. The proliferation and apoptosis of AML cells were detected using CCK-8 and flow cytometry. Results Differentially expressed miRNAs were identified using bioinformatics analysis, and miR-381-3p was ultimately determined as the study molecule. A total of 90 AML patients were included. The expression level of miR-381 in AML patients was lower than that in the control group, and all FAB subtypes were lower than those in the normal group. The expression level of miR-381 was not related to the age, gender, peripheral blood leukocytes, lymphocytes, and FAB typing of AML patients, and the OS and DFS of miR-381 patients with high expression were significantly prolonged, with statistically significant differences.In vitroexperiments had shown that knocking down miR-381 could inhibit apoptosis and promote proliferation of AML cells. Overexpression of miR-381 could promote apoptosis and inhibit proliferation of AML cells. Conclusion MiR-381-3p is low expressed in AML patients, and its overexpression can significantly prolong OS and DFS. miR-381-3p can promote apoptosis of AML cells, inhibit proliferation, and may become a targeted molecule for the treatment of AML.