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The water lily (Nymphaea tetragona) is an ancient angiosperm that belongs to the Nymphaeaceae family. As a rooted floating-leaf plant, water lilies are generally cultivated in fresh water, therefore, little is known about their survival strategies under salt stress. Long-term salt stress causes morphological changes, such as the rapid regeneration of floating leaves and a significant decrease in leaf number and surface area. We demonstrate that salt stress induces toxicity soon after treatment, but plants can adapt by regenerating floating leaves that are photosynthetically active. Transcriptome profiling revealed that ion binding was one of the most-enriched GO terms in leaf-petiole systems under salt stress. Sodium-transporter-related genes were downregulated, whereas K+ transporter genes were both up- and downregulated. These results suggest that restricting intracellular Na+ importing while maintaining balanced K+ homeostasis is an adaptive strategy for tolerating long-term salt stress. ICP-MS analysis identified the petioles and leaves as Na-hyperaccumulators, with a maximum content of over 80 g kg−1 DW under salt stress. Mapping of the Na-hyperaccumulation trait onto the phylogenetic relationships revealed that water lily plants might have a long evolutionary history from ancient marine plants, or may have undergone historical ecological events from salt to fresh water. Ammonium transporter genes involved in nitrogen metabolism were downregulated, whereas NO3−-related transporters were upregulated in both the leaves and petioles, suggesting a selective bias toward NO3− uptake under salt stress. The morphological changes we observed may be due to the reduced expression of genes related to auxin signal transduction. In conclusion, the floating leaves and submerged petioles of the water lily use a series of adaptive strategies to survive salt stress. These include the absorption and transport of ions and nutrients from the surrounding environments, and the ability to hyperaccumulate Na+. These adaptations may serve as the physiological basis for salt tolerance in water lily plants. [ABSTRACT FROM AUTHOR]