The relative configuration of the marine sesquiterpenoid oxyfungiformin, isolated from the soft coral Capnella fungiformis, was confirmed by synthesis using the natural product guaiol as chiral precursor. The absolute configuration of oxyfungiformin could be assigned by combination of X-ray diffraction and comparison of the values for the specific optical rotation. Oxyfungiformin and a diastereoisomer showed cytotoxic activity in cells originating from cancers of the lung, breast, and cervix.