<p>Acute myeloid leukemia (AML) is a highly heterogeneous malignancy originating from prolonged abnormal proliferation of immature myeloid cells. Long non-coding RNAs (lncRNAs) are important regulators of AML progression. TMEM147-AS1 has been reported to be abnormally expressed in AML. This study aimed to further explore the roles of TMEM147-AS1 in AML and the possible mechanism. The expression of TMEM147-AS1 and miR-873-3p and its role in the clinical progression of AML were investigated. The diagnostic and prognostic value of TMEM147-AS1 in AML was assessed. The impacts of TMEM147-AS1 on AML cell function were examined. And the targeting relationship among TMEM147-AS1, miR-873-3p, and ZFX was predicted by databases and verified by dual-luciferase reporter assay. TMEM147-AS1 was upregulated in AML tissues and cell lines. High TMEM147-AS1 expression was significantly related to adverse karyotype, shorter overall survival time, and worse prognosis in AML patients. And TMEM147-AS1 can distinguish AML patients from healthy individuals with relatively high sensitivity and specificity. Furthermore, TMEM147-AS1 targeted miR-873-3p, which further targeted ZFX. TMEM147-AS1 promoted proliferation and inhibited apoptosis of AML cells through downregulating the inhibitory effect of miR-873-3p on ZFX expression. TMEM147-AS1 promotes AML progression via regulating the miR-873-3p/ZFX axis. TMEM147-AS1 is a promising diagnostic and prognostic indicator in AML.</p>