Abstract: Nanoceria, as the most important nano-sized rare earth oxide, is widely used in various fields. With the increase of its use, people are more likely to be exposed to nanoceria, and the concerns about its biological safety gradually attract more attention with increasing controversies over its impacts on environmental and human health. At present, both positive and negative effects are reported when it comes to biological effects of nanoceria. This review overviewed the interaction between nanoceria and reactive oxygen species as well as related effects on DNA damage, autophagy, and mitogen-activated protein kinase (MAPK) pathway. This review focused on cytotoxicity and possible mechanism of nanoceria in order to provide a scientific basis for human health safety assessment.