Abstract: Algae are important primary producer in aquatic ecosystems and play an important role in the process of material conversion and energy migration. Programmed cell death (PCD) is a self-regulated cell death mode that is controlled by different signaling pathways. Studies have found that when algae are subjected to environmental stress, the algal cells exhibit PCD characteristics in morphology and physiology, accompanying with the changes of reactive oxygen species/nitric oxide/calcium ions (ROS/NO/Ca²⁺) levels. The researchers speculated that ROS/NO/Ca²⁺ maybe be a signaling molecule to mediate the changes of Caspase-like enzyme activity in algae cells and trigger a process similar to programmed cell death. However, little is known about how signaling molecules trigger a process similar to PCD in algae cells under environmental stress. This paper reviews the research progress of signal molecule ROS/NO/Ca²⁺ mediating the process similar to PCD in algae cells and the cascade effect between signal molecules. Finally, future research in this field similar to PCD is prospected.