In recent decades, microRNAs (miRNAs) have been considered novel gene regulators. Dysregulated miRNAs serve crucial roles in the formation and progression of acute myeloid leukaemia (AML). Therefore, the roles of differentially expressed miRNAs in AML require extensive investigation to obtain insight into the treatment of patients with AML. The present study demonstrated significant miR‑339‑5p downregulation in AML samples and cell lines. miR‑339‑5p overexpression attenuated AML cell proliferation by inducing cell cycle arrest and promoting cell apoptosis. Additionally, sex‑determining region Y‑related high‑mobility group box 4 (SOX4) was identified as a direct target gene of miR‑339‑5p in AML. Furthermore, SOX4 expression was significantly upregulated in AML samples; this upregulation was inversely correlated with the expression levels of miR‑339‑5p. Additionally, a series of rescue experiments demonstrated that SOX4 resumption reversed the effects of miR‑339‑5p overexpression on cell proliferation, cycle status and apoptosis of AML. In conclusion, miR‑339‑5p may serve its antiproliferative role in AML by directly targeting SOX4, which suggests that miR‑339‑5p may be considered an effective novel therapeutic target for treating patients with such an aggressive haematological malignancy.