An extensive study of the diterpenoids produced by the species of Isodon rubescens, has led to the isolation of 12 new ent-kaurane diterpenoids, hebeirubescensins A–L (1–12), and 19 known analogues. Their structures were determined on the basis of spectroscopic analysis. Selected compounds were assayed for their inhibitory ability against human A549, HT-29, and K562 cells. Among them, hebeirubescensins B and C exhibited significant cytotoxicity with IC50 values of <2.0 mM. The structure–activity relationships were discussed.