The existence of stable, transcriptionally silent human immunodeficiency virus (HIV) in latently infected cells represents a major obstacle to acquired immune deficiency syndrome (AIDS) therapy. Histone deacetylase (HDAC) can inhibit histone acetylation, resulting in HIV-1 provirus transcription silence. Apicidin, a widely used antiparasitic drug, exhibits antiparasitic activity by inhibiting HDAC. Using the latently infected A10.6 cell line, we describe the dose- and time-dependent manner in which Apicidin reverses HIV-1 latency. We found that Apicidin can synergize with trichostatin A (TSA) to activate HIV-1 gene expression. Chromatin immunoprecipitation (ChIP) assay further indicates that Apicidin induces HIV-1 reactivation by increasing the acetylation levels of H3 and H4 at nucleosome 1 in HIV-1 long terminal repeats (LTR). Our research reveals a potent activator for reactivating latent HIV-1 and shows promise for HIV-1 therapy.