The study of the effects of radionuclides and metals on organisms is necessary for the evaluation of their toxicity and their ecological threats. We first aimed to study the impacts of cadmium (Cd) and Uranium (U) on different biological levels of the crayfish Procambarus clarkii after acute and chronic exposures. We evaluated their impacts on mitochondria, oxidative stress responses, on histological structures, and the survival rates. We tried to connect these effects between them and to the bioaccumulation in the gills and the hepatopancreas. We also tried to discriminate the chemo and the radiotoxicity of U by exposing crayfish to either depleted or enriched U (233U: presenting a higher specific activity) using the same criteria of effects. We demonstrated that the gene mt encoding for the metallothionein was always over-expressed in the presence of Cd. Therefore, it seems to be a good biomarker of Cd toxicity in P. clarkii. The follow up of mitochondrial genes expressions (12s, atp6 and cox1), showed that both metals affect mitochondria and that their mechanisms of action do not seem to be always the same. We also observed that U generates more oxidative stress than Cd when comparing the expression levels of genes encoding for antioxidants (sod (Mn) and mt) and the enzymatic activities of superoxide dismutase, the catalase, the glutathione peroxidase and the glutathione S transferase. However, the symptoms of histo-pathological damages after Cd and U contamination were similar in both conditions. After comparing the survival rates of the crayfish, we concluded that Cd was more toxic than the radioelement. Moreover, we demonstrated that the toxic effect of U on P. clarkii exposed to a low environmental concentration is mainly due to its chemotoxicity rather than to its radiotoxicity. We established that, the molecular answers vary according to the intensity and the duration of the chemical stress applied to the organisms. We suggested the use of the expressions of all the studied genes as biomarkers of toxicity of U rather than the enzymatic activities because of their sensitivity. This work proposes mechanisms of actions of U based especially on the molecular responses and confirms the necessity of studying the ecotoxicological profile of this radioelement.