The concentration of heavy metals in the environment is increasing predominantly due to anthropogenic activities such as mining and other industrial activities. Exposure to metals above a certain threshold level induces deleterious effects in the living organisms. To survive such harsh environment, microbes possess a range of tolerance mechanisms and express stress-responsive genes and/or antioxidant enzymes to detoxify the metal stress.Protozoans, especially ciliates, are highly sensitive to the environmental changes, thereby making them suitable model systems for ecotoxicological studies. Thus, in the present work, the effect of heavy metals such as cadmium and copper has been studied in the freshwater ciliate, Euplotes aediculatus. This study focuses on the activity of antioxidant enzymes namely catalase and glutathione peroxidase in E. aediculatus under the heavy metal stress. Also, the expression of stress-responsive genes; heat-shock protein 70 (hsp70) and catalase (cat), has been studied after metal exposure. It was observed that the enzyme activity and the expression of these genes increased with an increase in the metal concentration and with the duration of metal exposure. Besides, these genes have been characterized to understand their role in cell defense. These genes of fresh water ciliate, therefore, can be used as molecular biomarkers to evaluate heavy metal toxicity.