Variations in precipitation and atmospheric N deposition affect water and N availability in desert and thus may have significant effects on desert ecosystems. Haloxylon ammodendron is a dominant plant in Asian desert, and addressing its physiological acclimatization to the changes in precipitation and N deposition can provide insight into how desert plants adapt to extreme environments by physiological adjustment. Carbon isotope ratio (δ13C) in plants has been suggested as a sensitive long-term indicator of physiological acclimatization. Therefore, this study evaluated the effect of precipitation change and increasing atmospheric N deposition on δ13C of H. ammodendron. Furthermore, H. ammodendron is a C4 plant; whether its δ13C can indicate water use efficiency (WUE) has not been addressed. In the present study, we designed a field experiment with a completely randomized factorial combination of N and water and measured δ13C and gas exchange of H. ammodendron. Then we calculated the degree of bundle-sheath leakiness (φ) and WUE of the assimilating branches of H. ammodendron. δ13C and φ remained stable under N and water supply, while N addition, water addition and their interaction affected gas exchange and WUE in H. ammodendron. In addition, δ13C had no correlation with WUE. These results were associated with the irrelevance between δ13C and the ratio of intercellular to ambient CO2 concentration (ci / ca), which might be caused by a special value (0.37) of the degree of bundle-sheath leakiness (φ) or a lower activity of carbonic anhydrase (CA) of H. ammodendron. In conclusion, δ13C of H. ammodendron is not sensitive to global change in precipitation and atmospheric N deposition and cannot be used for indicating its WUE.