Colorectal cancer (CRC) is the third most common cancer worldwide. Traditionally, chemotherapy for CRC is mainly targeting on inducing apoptosis. However, the chemo-resistance and defective in apoptosis induction have become prevalent. Thus it may have important therapeutic implications to exploit novel anticancer drugs to trigger nonapoptotic programmed cell death. Indeed, nonapoptotic cell death is considered a novel strategy to overcome drug resistance, because in most cases drug resistance results from evasion and insensitivity to apoptosis. Currently, accumulating evidence shows that phytochemicals with diverse chemical structures and pharmacological effects serve as safe and effective agents against drug resistance via triggering nonapoptotic cell death in cancer cells. In this concise chapter, we summarize the developments of nonapoptotic cell death triggering by phytochemicals in cancer cells. Understanding the role of phytochemicals in regulating nonapoptotic cell death will provide prospective strategies for cancer resistant therapy, with a focus on CRC.