Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long non-coding RNA, has been documented to be a new prognostic marker and gene regulator in several types of cancer, but its potential involvement in acute myeloid leukemia (AML) remains unclear. This study investigated the expression and functional role of MALAT-1 in AML. MALAT-1 expression was assessed by real-time quantitative PCR. After lentiviral-mediated MALAT-1 knockdown, the proliferation of AML cells was determined by CCK-8 and colony formation assays. Cell cycle progression and apoptosis were evaluated by flow cytometry and the expression of caspase-3, -8 and -9 was assessed by western blot analysis. We found that MALAT-1 expression in patients with acute monocytic leukemia (M5) was significantly increased when compared with that of healthy controls, and the overall survival of M5 patients with high MALAT-1 expression was markedly reduced when compared with the overall survival of patients with low MALAT-1 expression. The analysis of cellular experiments showed that MALAT-1 silencing decreased the proliferation of M5 cells (U-937 and THP-1), inhibited cell cycle progression and increased apoptosis. Taken together, these findings suggest that high MALAT-1 expression is closely associated with poor prognosis in M5 patients and may play a role in leukemia cell proliferation and apoptosis, and may serve as a promising theranostic marker.