Abstract Rice bacterial blight, caused by Xanthomonas oryzae pv. Oryzae ( Xoo ), threatens plant growth and yield. However, the molecular mechanisms underlying rice immunity against Xoo remain elusive. Here, we demonstrated down-regulation of a NAC (NAM-ATAF-CUC) transcription factor OsNAC2 enhanced resistance to bacterial blight disease in rice. Consistently, salicylic acid (SA) biosynthesis was greatly attenuated when OsNAC2 overexpressed. Furthermore, study demonstrated that OsNAC2 can down-regulated the expression of SA synthesis genes, thus mediating SA signal transmission. Simultaneously, OsNAC2 interacted with OsEREBP1 (AP2/ERF family) in the nucleus, may be bloking the inhibition of OsNAC2 to OsICS1 , OsPAL3 and so on. Furthermore, OsEREBP1 interacted with OsXb22a in the cytoplasm to exert its positive regulatory effects to bacterial blight. However, OsNAC2 -overexpression kept OsEREBP1 in the nucleus and be rapidly degraded in pathogen infection, which adversely affects the interaction of OsEREBP1-OsXb22a. Our results determined that OsNAC2 inhibits the SA signaling and stably interacts with OsEREBP1 to maintain disease resistance. This OsNAC2-OsEREBP1-based homeostatic mechanism provides new insights into rice disease resistance, and it may be useful for improving the disease resistance of important crops through breeding.