The $CH_2Cl_2$ soluble part of the leaves of Helianthus tuberosus L. (Compositae) exhibited a potent cytotoxic activity against the cultured human tumor cell lines including A-549, SK-OV-3, SK-MEL-2, XF498 and HCT-15 in vitro. Bioassaydirected fractionation of the $CH_2Cl_2$ soluble part of this plant led to the isolation of four cytotoxic sesquiterpene lactones having ${alpha}$-methylene-${gamma}$-lactone ring in the molecule. On the basis of physical and spectral evidences, their structures were characterized as ${Delta}^{4,15}$-isoatripliciolide tiglate (1), ${Delta}^{4,15}$-isoatripliciolide methacrylate (2), budlein A isobutylate (3) and budlein A tiglate (4). The ${Delta}^{4,15}$-isoatripliciolide tiglate (1) showed the most potent cytotoxic activity ($0.26{mu}M