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Background: Salicornia neei is a halophyte plant that has been proposed for phytoremediation of saline wastewater generated by land based aquaculture, which usually contains elevated concentrations of ammonium resulting from protein metabolism. To identify the molecular mechanisms related to ammonium response through of analysis results in silico and the Michaelis Menten ammonium removal biokinetics and the transcriptome of S. neei in response to growth in saline water containing 3 mM ammonium. Results: The parameters for ammonium uptake by S. neei root cuttings were estimated: 1) maximum uptake rate Imax = 6.91+/-0.32 mM N g−1 fresh weight h−1; and 2) half-saturation constant Km= 0.807+/-0.142 mM N L−1. Further, a total of 45,327 genes were annotated, which represents 51.2% of the contig predicted from de novo assembly. A total of 9,140 genes were differentially expressed in response to ammonium in saline water, but only 7,396 could be annotated against functional databases. According to the GO enrichment and as well as KEGG pathway analyses showed these upregulated genes were involved in pr cellular anatomical entity, cellular process, and metabolic process, including biological KEGG pathways linked to biosynthesis amino acid biosynthesis, nitrogen metabolism and autophagy and other. In addiction, a set of 72 genes were directly involved in ammonium metabolism, including glutamine synthetase 1 (GLN1), glutamate synthase 1 (GLT1), and ferredoxin-dependent glutamate synthase chloroplastic (FdGOGAT). Conclusion: Our results support the hypothesis that an ammonium detoxification system mediated by glutamine and glutamate synthase was activated in S. neei when exposed to ammonium and saline water. These results provide novel insight into understanding the molecular mechanisms of ammonium nutrition and aid for investigating the response of halophyte plants to saline wastewater from land-based aquaculture