The histone acetyltransferase complex HBO1 (KAT7) is an oncogenic regulator across multiple cancers, promoting cell proliferation and migration. Though clinically important, no targeted therapies address HBO1 dysregulation. HBO1 forms complexes with MEAF6, JADE(1/2/3), ING(ING4/5), and BRPF1/2/3 to acetylate histones H3 and H4, especially at H3K14, promoting transcriptional activation and genomic stability. It colocalizes with active transcriptional sites and participates in gene regulation, DNA repair and replication. Most HBO1-associated cancer mutations are missense, though their effects remain unclear. Silencing HBO1 restores normal proliferation and gene expression, underscoring its oncogenic role. HBO1 activity supports cancer pathways, including apoptosis resistance, DNA damage response, and cell cycle regulation. The HBO1 inhibitor WM-3835 disrupts H3K14 acetylation, reducing tumor growth in several cancers. This review provides insights into the function of HBO1 in cancer, especially in histone acetylation, ubiquitination, stem cell maintenance, and pro- and anti-oncogenic signaling. Understanding the roles of HBO1 may guide new epigenetic therapies for HBO1-driven malignancies.