Radiotherapy (RT) is currently one of the leading treatment for various cancers and it may cause injury to healthy tissue, with both short-term and long-term side effects. Inflammatory responses play an important role in the adverse reactions of early and late ionizing radiation. Nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) inflammasome as a multi-protein complex that activates caspase-1 can give rise to the proinflammatory cytokines such as interleukin-18 (IL-18) and interleukin-1 beta (IL-1β) maturation. Recent experiments and studies have shown that up-regulation of NLRP3 inflammasome have a big impact on radiation damage, which include radiation-induced oral mucositis, radiation-induced skin reactions, radiation-induced lung damage, radiation-induced intestinal injury and radiation-induced changes in other systems. In this paper, we will review the role of NLRP3 inflammasome in radiation damage, to explore possible therapeutic strategies for radiation damage.