Investigation of the aerial parts of Vernonia triflosculosa afforded three hirsutinolides of which 8α-(4α-hydroxymethacryloyloxy)-10α-hydroxy-1,13-dimethoxy-hirsutinolide is new, three ent-kaurane diterpenes, among which the 19-[α-l-arabinopyranosyl-(1 → 2)-β-d-glucopyranosyl] esters of 16β-hydroxy-ent-kauran-19-oic acid and of 16β,17-hydroxy-ent-kauran-19-oic acid are also new. Diterpenes are reported here for the first time in the large genus Vernonia. Their structures were elucidated using 1D and 2D NMR measurement as well as ESI, CIMS, and HRMS analysis. Two hirsutinolides were studied for their NF-κB DNA binding activity in HaCaT cells (a human cell line similar to keratinocytes) and for their inhibition on IL-8 production in HeLa cells.