Abstract: To explore the toxicity of dihydroartemisinin (DHA) to Tetrahymena thermophila, T. thermophila was exposed to DHA (0, 40, 80, 160 and 320 μmol/L), and then cell proliferation, cell structures and movement, antioxidase activity, and mitochondrial membrane potential (MMP) were measured. The results showed that DHA inhibited the growth of T. thermophila in a concentration-dependent pattern. Observation through inverted microscope showed that after 48h treatment with DHA, T. thermophila became round and shrunken compared with the cells in the control group, which were oval. Meanwhile, high concentration treatment group (160 and 320 μmol/L) reduced cell movement, induced nucleus pycnosis, and decreased MMP significantly (P<0.05). With the increase of DHA concentration, the activities of the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST) increased at first and then decreased, and the level of succinate dehydrogenase (SDH) decreased significantly (P<0.05). The results indicated that the antioxidant enzymes in T. thermophila could prevent the oxidative damage caused by DHA exposure. Based on our results, the toxic effects of DHA on T. thermophila might be related with oxidative damage and mitochondrial damage.