Thirty-two methanol extracts of thirty-one Vietnamese medicinal plants were evaluated for the cytotoxic activity against five human cancer cell lines, including A549, MCF-7, HT 1080, Huh-7, and HepG2. Of these, the nine extracts of Acanthopanax trifoliatus (4), Acanthopanax gracilistylus (5), Siegesbeckia orientalis (10), Betula alnoides (11), Passiflora edulis (18), Zanthoxylum simulans (leaf, 23), Adenosma caeruleum (26), Solanum verbascifolium (29), and Alpinia malaccensis (31), exhibited high potent cytotoxic activity showing a certain degree of selectivity against the different cell types, with $IC_{50}$ values ranging from 2.1 to $3.8;{mu}g/mL$.