Fifteen diterpenoids (1 -15), including three undescribed ones with ent-atisane skeleton, eupnerias G -I (1 -3), were obtained from Euphorbia neriifolia. Compounds 1-3 were established through comprehensive spectroscopic analysis. Compounds 4 and 5 exhibited obvious anti-HIV-1 effect, and their EC 50 were 6.6 � 3.2 and 6.4 � 2.5 μg mL À 1 , respectively. Compound 6 exhibited moderate cytotoxicity on HepG2 and HepG2/Adr cells with IC 50 at 13.70 and 15.57 μM, respectively. In addition, compound 15 exhibited significant cytotoxicity on HepG2 cell lines (IC 50 = 0.01 μM), while it did not show any cytotoxicity against HepG2/Adr cell lines.