Abstract: A deep understanding of radiobiology theory is essential for studying the effects of radiation. Radiation bystander effect (RIBE) has become a research hotspot in the field of radiobiology since its discovery. The direct and indirect effects of radiation on targeted and non-targeted cells, tissues, and organs profoundly affect the progress and outcome of radiotherapy for malignant tumors. Up to now, a large number of experimental studies have been conducted in vitro and in vivo to reveal the mechanism of RIBE. The exogenous mediators generated by radiation migrate into the adjacent tissues or cells, stimulating the activation of various signaling pathways, leading to immune and inflammatory responses, epigenetic regulation, and radiation-induced carcinogenic transformation. This paper reviews the research status and mechanism of RIBE in order to provide a theoretical basis for the development of new drugs for radiation protection and improvement of radiotherapy efficacy.