Abstract: The forkhead box O (FoxO) transcription factor family plays an important role in cell functions, including metabo-lism, apoptosis, cellular proliferation, stress reactions, DNA repair, and immune response. As a member of this family, forkhead box O3a (FoxO3a) regulates its target genes by modulating histone modifications, including phosphorylation, acetylation, and methylation. FoxO3a expression is abnormally downregulated in urologic neoplasm. Protein modifications and FoxO 3a activity are mainly con -trolled by PI3K/Akt signal pathway and other signaling pathways. FoxO 3a is also involved in the initiation, progression, and prognosis of urologic neoplasm. This review focuses on the function of FoxO 3a in urologic neoplasm and elucidates the regulatory mechanisms involved. This article will provide novel strategies to clinical diagnosis and drug therapy of urologic neoplasms.