Post-translational histone modifications such as histone acetylation play essential roles in plant growth, development, and stress responses by modulating gene expression. However, little is known about epigenetic regulation in plant secondary metabolism. To analyze the involvement of histone acetylation in elicitor-induced metabolite production, ginseng adventitious roots were treated with methyl jasmonate (MeJA) together with histone deacetylase (HDAC) inhibitors. Western blot results revealed that HDAC inhibitors cause hyperacetylation of histone H3, especially acetylation of histone H3 lysine 18, under MeJA treatment. In addition, the HDAC inhibitor-induced increase in the transcript levels of MeJA-induced ginsenoside biosynthetic genes resulted in enhancement of MeJA-induced ginsenoside production, indicating that HDAC activity serves as a negative factor in MeJA-induced transcriptional induction of ginsenoside biosynthesis pathways. In addition, we identified 25 HDAC genes from the ginseng genome, which suggested that MeJA-induced PgHDACs (PgHDA05, PgHDA10, PgHDA16, PgHDA17, PgHDA18, PgHDA19, and PgHDA20) might be key factors controlling MeJA-induced ginsenoside production in ginseng adventitious roots. This unique information regarding histone acetylation and ginsenoside production would be helpful in understanding epigenetic regulation in plant secondary metabolism.