Transcription factor NAC78 cooperates with NAC78 interacting protein 6 to confer drought tolerance in rice. Plant physiology NAC (NAM, ATAF1/2, and CUC2) family transcription factors are involved in several cellular processes, including responses to drought, salinity, cold, and submergence. However, whether or how certain NAC proteins regulate drought tolerance in rice (Oryza sativa) remain unclear. In this study, we show that overexpression of OsNAC78 enhanced rice resistance to drought treatment, whereas Osnac78 mutant plants were susceptible to drought stress. We further characterized the OsNAC78 interacting protein, named NAC78 interacting protein 6 (OsNACIP6), and found that it conferred rice drought tolerance. Our results demonstrate that OsNACIP6 enhanced the transcription of OsNAC78 and promoted the expression of its downstream target OsGSTU37, encoding a glutathione reductase. The ABRE4 cis-element in the promoter region of OsNACIP675-1-127 conferred significant upregulation of OsNACIP6 expression and initiated the OsNACIP6/OsNAC78-OsGSTU37 module that facilitates rice growth under drought conditions. Together, our results uncover a transcriptional module composed of OsNACIP6, OsNAC78, and OsGSTU37 and provide insights into the molecular mechanisms underlying the drought stress response in rice. 10.1093/plphys/kiae395