In this study, three different sizes of cerium oxide ($CeO_2$) nanoparticles were synthesized and exposed to Caenorhabditis elegans to investigate the potential harmful effect of $CeO_2$ nanoparticles on the environment. The effects of the $CeO_2$ nanoparticles on C. elegans were assessed at multiple levels, such as with respect to stress response gene expression, growth, reproduction and mortality. Moreover, to test the ecotoxicological relevance of $CeO_2$-induced gene expression. The overall results suggest that $CeO_2$ nanoparticles may provoke ecotoxicity in C. elegans especially with respect to gene expression, reproduction and survival, which can comprise an important contribution to knowledge on the ecotoxicity of $CeO_2$ nanoparticles, about which little data are available. This is particularly valuable in the biomarker research on ecotoxicology, as ecological relevance is a crucial criterion for the applicability of the biomarker in field biomonitoring and ecological risk assessment.