When the body suffered from stimuli in vivo and in vivo, such as cerebral ischemia or organ damage, in order to maintain the homeostasis, the system will first perform adaptive regulation at the organelle level, including stress response in the endoplasmic reticulum and mitochondrial protein folding reaction. If the environmental imbalance cannot be maintained, apoptosis will begin in order to regulate the cell at the overall level. In this process, endoplasmic reticulum-mitochondrial stress bi-directional regulatory mechanism played an important role. The review was to explore endoplasmic reticulum-mitochondrial stress bi-directional regulatory mechanism. The mechanism of endoplasmic reticulum -mitochondrial bi-directional regulation and the relationship between endoplasmic reticulum and mitochondria was discussed in this paper. The research progress of narcotic drugs was analyzed to provide a new idea for organ protection and reasonable use of anesthetics in the future.