Background <p><i>Hernandia nymphaeifolia</i> is a typical mangrove associate with high ecological, ornamental, and medicinal values, but in China, it has become endangered in recent years, and an urgent protection is needed. Salinity is a key factor for growth and survival of mangrove seedlings, and thus a comprehensive understanding of salt tolerance in mangroves is important for their conservation and afforestation. However, little is known regarding salt-responsive mechanisms in <i>H. nymphaeifolia</i>.</p> Results <p>In this study, we posed gradient salt treatments on <i>H. nymphaeifolia</i> seedlings and investigated their physiological and transcriptional reprogramming in response to salinity stress. The results revealed that hyper-salinity stress adversely impacted on leaf growth, cell integrity and photosynthetic performance of <i>H. nymphaeifolia</i> seedlings than those growing in fresh water or low salt conditions, mirroring its moderate salinity tolerance as a mangrove associate. Genes involved in osmotic sensing and regulation, reactive oxygen species (ROS) scavenging and ion homeostasis were differentially expressed to alleviate the destructive effects. Furthermore, our results identified some kinase-encoding genes as hub genes in co-expression networks, which may play a key role in regulating the synergistic expression of salt-responsive genes upon stress conditions.</p> Conclusion <p>This research enriches our knowledge of the molecular mechanisms underlying the salinity tolerance of mangrove associates, which can theoretically assist the conservation and restoration of <i>H. nymphaeifolia</i>. Our findings also provide valuable genetic resources for future potential bioengineering applications in the fields of agriculture and forestry.</p>