Egicoccus halophilus EGI 80432(T), a halotolerant bacterium isolated from a saline-alkaline soil, belongs to a member of the class Nitriliruptoria, which exhibits high adaptability to salt environments. At present, the detailed knowledge of the salinity adaptation strategies of Nitriliruptoria was limited except for one research by using comparative genomics analysis. Here, we investigated the salinity adaptation mechanism of E. halophilus EGI 80432(T) by comparative physiological and transcriptomic analyses. The results of physiological analyses showed that trehalose and glutamate were accumulated by salt stress and showed the maximum at moderate salinity condition. Furthermore, the contents of histidine, threonine, proline, and ectoine were increased with increasing salt concentration. We found that both 0% and 9% NaCl conditions resulted in increased expressions of genes involved in carbohydrate and energy metabolisms, but negatively affected the Na+ efflux, iron, and molybdate transport. Moreover, the high salt condition led to enhancement of transcription of genes required for the synthesis of compatible solutes, e.g., glutamate, histidine, threonine, proline, and ectoine, which agree with the results of physiological analyses. The above results revealed that E. halophilus EGI 80432(T) increased inorganic ions uptake and accumulated trehalose and glutamate in response to moderate salinity condition, while the salinity adaptation strategy was changed from a "salt-in-cytoplasm" strategy to a "compatible solute" strategy under high salinity condition. The findings in this study would promote further studies in salt tolerance molecular mechanism of Nitriliruptoria and provide a theoretical support for E. halophilus EGI 80432(T)'s application in ecological restoration. Key Points center dot Salt stress affected gene expressions responsible for carbohydrate and energy metabolisms of E. halophilus EGI 8042(T). center dot E. halophilus EGI 80432(T)significantly accumulated compatible solutes under salt stress. center dot E. halophilus EGI 80432(T)adopted a "compatible solute" strategy to withstand high salt stress.