The red-eared slider (Trachemys scripta elegans), a freshwater turtle, is an invasive species in many parts of the world where it survives in both freshwater and coastal saline habitats. High salinity can induce reactive oxygen species (ROS) production and lead to oxidative damage. In this study, we investigate the antioxidant defense mechanisms of T. s. elegans in response to salinity stress. The results showed that the mRNA expression levels of superoxide dismutase (SODs), catalase (CAT) and glutathione peroxidase (GSH-PXs) were significantly increased in both 5 psu and 15 psu groups at the early stages of salinity exposure (generally 6-48 h), but typically returned to control levels after the longest 30 d exposure. In addition, hepatic and cardiac mRNA levels of the NF-E2-related factor 2 (Nrf2), showed a similar upregulation as an early response to stress, but decreased at 30 d in the 5 psu and 15 psu groups. The mRNA levels of the negative regulator of Nrf2, kelch-like ECH associating protein 1 (Keap1), exhibited the opposite pattern. Moreover, mRNA expression levels of target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1) in liver and heart showed roughly similar patterns to those for Nrf2. Furthermore, the content of malondialdehyde (MDA) was significantly increased in liver, especially in the 15 psu group by ~2.5-fold. Taken together, these results indicate that T. s. elegans may activate the TOR-Nrf2 pathway to modulate antioxidant genes transcription in order to promote enhanced antioxidant defense in response to salinity stress.