Ceria nanoparticles were classified as nanozymes because they are able to mimic the activities of some natural enzymes such as superoxide dismutase (SOD), catalase, oxidase and photolyase under given conditions. These functions have driven studies to explore the factors that could promote ceria nanoparticle enzyme activities. Accordingly, factors including size, shape, exposed plane and surface coating that could modulate the enzymatic activities of ceria nanoparticles have been explored. In the present study, we investigated the relationship between ceria nanoparticle crystallinity and SOD-like activity. Two groups of ceria nanoparticles with sizes of several nanometers and tens of nanometers in each group were synthesized with different crystallinities. The ceria nanoparticle crystallinities were closely connected to their Ce 3 + /Ce 4 + ratio, where the lower crystallinity resulted in a higher Ce 3 + concentration and vice versa. The catalytic activity evaluation results indicated that the nanoparticles featuring lower crystallinity exhibited higher SOD-like activity even though the nanoparticles had a smaller specific surface area. The crystallinity-dominated SOD-like activity variation could be sensed by cells, as the nanoparticles featuring lower crystallinity could better protect the cells from paraquat-induced oxidative stress. Therefore, decreasing crystallinity could be an effective way to achieve highly active ceria nanoparticles for SOD-related biological applications.