Eudesmols are naturally occurring sesquiterpenoid alcohols that present cytotoxic effect to cancer cells. Herein, all eudesmol isomers displayed cytotoxicity to different tumour cell lines. a-Eudesmol showed IC50 values ranging from 5.38 1.10 to 10.60 1.33 lg/mL for B16-F10 and K562 cell lines, b-eudesmol showed IC50 values ranging from 16.51 1.21 to 24.57 2.75 lg/mL for B16-F10 and HepG2 cell lines, and c-eudesmol showed IC50 values ranging from 8.86 1.27 to 15.15 1.06 lg/mL for B16-F10 and K562 cell lines, respectively. In addition, in this work, we studied the mechanisms of cytotoxic action of eudesmol isomers (a-, b- and c-eudesmol) in human hepatocellular carcinoma HepG2 cells. After 24-hr incubation, HepG2 cells treated with eudesmol isomers presented typical hallmarks of apoptosis, as observed by morphological analysis in cells stained with haematoxylin–eosin and acridine orange/ethidium bromide. None of eudesmol isomers caused membrane disruption at any concentration tested. Moreover, eudesmol isomers induced loss of mitochondrial membrane potential and an increase in caspase-3 activation in HepG2 cells, suggesting the induction of caspase-mediated apoptotic cell death. In conclusion, the eudesmol isomers herein investigated are able to reduce cell proliferation and to induce tumour cell death by caspase-mediated apoptosis pathways.