| Summary: | The roots of <i>Euphorbia fischeriana</i> have been used as a traditional Chinese medicine for the treatment of tuberculosis and ringworm. In the current study, diterpenoids from the ethyl acetate extract of the roots <i>E. fischeriana</i> and their cytotoxic effects against five cancer lines were investigated. Two new <i>ent</i>-abietane diterpenoids, euphonoids H and I (<b>1</b>–<b>2</b>), as well as their two analogues (<b>3</b>–<b>4</b>) were first isolated from this source. The structures of the two new compounds were elucidated on the basis of spectroscopic data and quantum chemical calculation. Their absolute configurations were assigned via ECD spectrum calculation. The isolated compounds were evaluated for their antiproliferative activities against five cancer cell lines. Compounds <b>1</b> and <b>2</b> exhibited significant inhibitory effects against human prostate cancers C4-2B and C4-2B/ENZR cell lines with IC<sub>50</sub> values ranging from 4.16 ± 0.42 to 5.74 ± 0.45 μM.
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