Cerium nanomaterials (CeNMs) are integrated in consumer products (e.g. wood stain, painting, fuel additive) because of their strong abrasive power, high resistance and UV-shielding properties. Given the production volumes of CeNMs and their potential release into the aquatic environment, assessment of the potential environmental risks of CeNMs is a priority. While the impacts of nanomaterials in freshwater have been studied this last decade, studies including the influence of environmental factors as salinity are scarce. Safety of nCeO2 should be considered because harmful effects have already been demonstrated. Studies are nevertheless controversial reporting either toxic effect, no apparent effect or even beneficial one. Most studied parameters were about behavioural changes, enzymatic reactions or cellular damages whereas gene expression level is poorly considered. Nevertheless molecular change is the first organism response to environmental modifications. In this context, the aim of the present study is to assess the fate, behaviour and toxicity effects of CeNM under different salinities using the euryhaline bivalve, Corbicula fluminea and a multi-marker approach at different levels (molecular and sub-cellular) of biological organization. The CeNMs included in a commercial fuel additive (Envirox™) at two stages of its life cycle and NM-212, a standardized CeNMs provided from the Joint Research Centre, suspended in water covering salinity from continent (1.5 psu) to esturaries (15 psu). The exposure was conducted under indoor pocked-size mesocosms during 28 days by injecting punctually 91 µg/L CeNMs to reach a final concentration of 1 mg/L. The size, shape and mineralogy of the uncombusted and combusted Envirox™ were performed by Transmission Electron Microscopy. Total Ce in the water column, labile forms of Ce and Ce contents in the bivalves were estimated by ICP-MS. Organisms were collected after 7, 14, 21 and 28 days. Biochemical responses (oxidative stress, cell damage, energetic reserves) were measured in the digestive gland using the spectrophotomer automate Konelab 20Xti. Gills were taken and stored until mRNA extraction for gene expression analysis by RT-qPCR. This analysis was done on 12 genes of interest involved in antioxidant and antitoxic reactions, general response to stress, autophagy or cell structure. All the biomarker data were analysed using a statistical model, LDA or PLS-DA analysis. The behaviour of the CeNMs in the water column was different according to the salinity and their coating. Results showed that digestive cellular damage and antioxidant defences were activated during a long term exposure. Global profiles of gene expression in gills appeared strongly different according to the salinity. Both Envirox™ exposures often induced responses different from the control but not significantly different between them. The originality of this study was not only the use of CeNMs directly extracted from commercial product or artificially aged, but also the multistress exposure combining salinity. Moreover, studying gene expression changes is an earlier way to detect ENMs impact.