A new aryl dihydronaphthalene lignan, echiumin E (<b>1</b>), and four known compounds, echiumin A, globoidnan A, (-)-rabdosiin, and rosmarinic acid (<b>2</b>-<b>5</b>), were isolated from the Australian invasive plant <i>Echium plantagineum</i> (Paterson's curse) for the first time. Echiumin E (<b>1</b>) was characterized by 1D/2D NMR spectroscopy and MS spectrometry, with its absolute configuration assigned through comparison of experimental and TDDFT-calculated ECD data. Echiumin E (<b>1</b>) along with compounds <b>3</b>-<b>5</b> were screened in vitro against three cancer cell lines (SH-SY5Y, HeLa, and PC-3) and a prostate stromal (normal) cell line (WPMY-1) using a resazurin reduction assay. Echiumin E (<b>1</b>) was found to be active toward HeLa cells (IC<sub>50</sub> 0.21 μM).