We performed temporary siRNA knockdowns of DR5 and DR4 in cancer of the colon cells. We showed that snake venom toxin inhibited development of cancer of the colon cells through induction of apoptosis. We also showed that the appearance of DR4 and DR5 was improved by treatment of snake venom order Linifanib toxin. . More over, knock-down of DR4 or DR5 reversed the result of snake venom toxin. Snake venom toxin also induced JNK phosphorylation and ROS generation, but, pre-treatment of JNK chemical and ROS scavenger reversed the inhibitory effect of snake venom toxin on cancer cell proliferation, and paid off the snake venom toxin induced upregulation of DR4 and DR5 expression. Our indicated that snake venom toxin could inhibit human colon cancer cell growth, and these effects may be related to JNK and ROS mediated activation of death receptor signals. Keywords: Snake venom killer, Apoptosis, Death receptor, ROS, JNK Back ground Colorectal cancer is one of the most pyrazine common fetal cancers, evoking the second cancer related death. . While a number of chemotherapeutic agents including capecitabine, irinotecan, oxaliplatin, and leucovorinmodulated fluorouracil have increased response rates to chemotherapy in advanced colorectal cancer, resistance to chemotherapy remains a major problem within the therapy of this cancer and new techniques are urgently required. Furthermore, it is reported that most chemotherapeutics have marked effects on normal cells. Recently, a human anatomy of research suggested that down-regulation or mutation of death receptors may be a mechanism by which cancer cells avoid destruction by the immune system. Apoptosis is the best characterized type of programmed cell death and is an intracellular suicide program owning morphologic traits and biochemical features, including chromatin condensation, nuclear DNA fragmentation, cell shrinkage, membrane blebbing, and the synthesis of apoptotic bodies. It PFT is definitely an crucial process in maintaining homeostasis which is often triggered by many facets like radiation and chemotherapeutics drugs. . Thus far, two major apoptotic pathways have already been referred to as follows: the intrinsic caused pathway and the extrinsic death receptor mediated pathway.. In the intrinsic pathway, proapoptotic proteins create a net increase of free cytosolic cytochrome C. Once introduced, cytochrome c interacts with adenosine triphosphate, apoptosis activating factor 1 and procaspase 9 to make the apoptosome. The apoptosome cleaves and activates caspase 9, leading to caspases 7 initial, thus stimulating apoptosis. The extrinsic apoptotic pathway stems at membrane death receptors such as DR4, and DR5 and Fas. In this extrinsic pathway, binding of tumor necrosis factor, TNF associated apoptosis inducing ligand, or Fas ligands for their receptors, in affiliation with adaptor molecules such as Fas associated death domain or TNF receptor associated death domain, contributes to cleavage and activation of initiator caspase 8 and 10, which in turn cleaves and activates executioner caspases 7 culminating in apoptosis.