Euphorbia Fisheriana Steudal (EF) and Saussurea Involucrata (SI) are rare plants which were used in ancient Eastern medicine. In this study, the antitumor properties of EF and SI were assessed by MTT assay, Western immunobloting, DNA fragmentation and nuclei staining methods. We have found that both of the plant extracts promote the apoptotic death of tumor cells by activation of proapoptotic regulators of Bcl-2 family and MAPK pathway, especially SAPK/JNK2. In case when EF was employed, the initiation of apoptosis was linked to the activation of intrinsic pathway and p38. No visible changes were detected in relation to ERK and JNK1. P38 inhibition and gene silencing by siJNK2 caused an inhibition of Bax and p53, at the same time procaspase-9 was distinctly up-regulated in contrast to caspase-9. Different outcome was observed after induction with SI. Apoptosis was triggered via activation of caspase-8 and caspase-9; no changes were detected in relation to p38 and ERK. The specific aspect of SI treatment was in inhibition of JNK1. Gene silencing by siJNK2 down-regulated Bax and p53; and up-regulated procaspase-9. These results suggest that EF and SI are potent inhibitors in the growth of cancer cells, and the apoptotic mechanism might be related to the activation of JNK2, rather than p38. Additionally, SI is an effective inhibitor of JNK1. Euphorbia Fisheriana Steudal and Saussurea Involucrata would be novel natural drugs nowadays, less toxic and with a higher cost benefit in comparison to chemical drugs in cancer treatment.