A growing body of evidence indicates that long non-coding RNA (lncRNA) is involved in the development and progression of many diseases. It has been reported that lncRNA LINC00467 is disregulated in multiple tumors, while its role in acute myeloid leukemia (AML) is still unknown. Here, we find that LINC00467 expression is significantly increased in AML specimens and cell lines. Further investigations show that knockdown of LINC00467 inhibits the malignant phenotypes of AML cells. Consistently, LINC00467 knockdown slows AML progression in immunodeficient mice. Interestingly, microRNA-339 (miR-339) is upregulated and its target gene SKI, an oncogene, is downregulated in AML cells after LINC00467 knockdown. More importantly, inhibition of miR-339 can largely abolish the effect of LINC00467 knockdown on AML cells. Collectively, our data demonstrate that LINC00467 plays an important role in the pathogenesis of AML by targeting the miR-339/SKI pathway, which provides a new sight for the subsequent treatment of AML.