Nanotechnology interest has considerably grown during last decades and nanoproducts are now part of our everyday life. Nanoparticle (NP) concentrations in natural environment are not yet known but releases during their life cycle are to consider. NP harmful effects have already been demonstrated on freshwater and marine species but their potential toxicity at more realistic low exposure concentration is still not well studied. Cerium dioxide nanoparticles (nCeO2) are listed in OECD priority list of manufactured nanomaterials for their assessment because of their large production making them available for widespread uses in daily products. They are used in different fields such as automotive or optic. Several studies highlighted that nCeO2 impact organism’s physiology by affecting oxidative defenses and cellular membrane stability while gene expression studies remain still scarce and especially among non-sequenced organisms.\nThe aim of the present work was to evaluate gene expression disturbance occurring in C. fluminea, a widespread freshwater bivalve, exposed during 28 days under indoor mesocosm to multistress conditions. Two salinities (1.5 and 15 PSU) were applied to cover a range of salinity from the continent to the estuaries and three NPs were selected in order to have both standardized and commercial NPs but also to mimic changes occurring after NP uses. Two studies were done on variation of 12 gene expression by RT-qPCR in gills and digestive gland according to the exposure conditions and time. Global profile of gene expression responses are clearly different according to the salinity and both organs selected were responding to NP contamination. Results obtained for NPs extracted from commercial product have highlighted the need of further studies using consumer available NPs. The second study was about comparing expression level of the 12 selected genes in both organs after 28 days in control organisms. Interestingly, tissues expression gene analysis revealed strong differences of expression level (>2 fold) for some genes in gills compared to digestive gland regardless to salinity. This work followed expression of 12 genes that showed expression variation according to medium salinity, organ or nCeO2. Studying gene expression changes is an earlier way to detect contamination impact. Genome sequencing of C. fluminea should allow to analyze more gene expression involved in other molecular pathway potentially impacted.