〔Abstract〕 Objective To investigate the expression of long noncoding RNA(LncRNAs) HOTAIR in acute myeloid leukemia(AML) and the function and molecular mechanism of resistance to daunorubicin(DNR) in AML cells. Methods The qRT-PCR was used to detect leukemia cell lines, primary acute myeloid leukemia cells, the normal expression level of control cells HOTAIR. U937 cells and THP1 cells were selected as research objects.The sh-NC plasmid and sh-HOTAIR plasmid of hairpin RNA(shRNA) were constructed and transfected into these two cells, respectively. The expression of HOTAIR in the cells was detected by qRT-PCR. P-glycoprotein(P-gp) expression in transfected cells was detected by Western blot,DNR(0.1 μmol/L) was applied to each cell, CCK8 assay was used to detect cell proliferation, and flow cytometry was used to detect cell apoptosis. Results The expression of HOTAIR in the normal control group was significantly lower than that in the leukemia cell line and the acute myeloid leukemia primary cells; The expression of HOTAIR in U937 cells and THP1 cells was successfully down-regulated, and the level of P-glycoprotein was also decreased. The expression of HOTAIR in U937 cells and THP1 cells was successfully down-regulated, combined with DNR was more conducive to inhibit cell proliferation and promote apoptosis. Conclusion The abnormal expression of HOTAIR in AML is involved in the formation of resistance to DNR.