Epigenetic modifiers are proved to be effective specialized products-mining tools by rationally regulating the gene expression of fungal biosynthetic pathways. Chemical investigation on the histone deacetylase inhibitor (HDI) vorinostat (also known as SAHA)-modified cultures of the basidiomycete Cyathus stercoreus (Schwein.) De Toni (Nidulariaceae) led to the isolation of nine previously undescribed sesquiterpenes, and four previously described ones. The structures of the nine undescribed compounds were determined by extensive NMR spectroscopic analysis, HRESIMS analysis, as well as ECD and NMR calculations. Notably, the isolated sesquiterpenes are exclusive or overproduced from the epigenetic modified cultures compared to the negative control cultures. Additionally, the skeleton types of the isolated sesquiterpenes include protoilludalane, illudalane, 1,11-seco-protoilludalane, 10,11-seco-illudalane, and 14(11→10)abeo-illudalane. It is noteworthy that the 14(11→10)abeo-illudalane skeleton is reported for the first time. Cystercorodiol A, 4-O-acetylcybrodol, cystercorotone, and cybrodol showed weak inhibitory activity against the bacterium Escherichia coli ATCC25922 with the inhibitory rates 34.7%, 33.0%, 32.3%, and 29.6% at the concentration 200 μM, respectively. This study suggested that epigenetic modifiers are also an effective tool for specialized metabolite-mining in basidiomycetes.