This study was aimed to deal with a comparative proteome analysis of the two rice genotypes with contrasting response to drought stress, N22 (drought-tolerant, DT) and IR64 (drought-sensitive, DS). Proteins were extracted from the root tissues collected from the control and drought stressed plants of both the genotypes. NanoLC-MS/MS analysis of the protein sample was performed using EASY-nLC 1000 system for the separation and identification of peptides/proteins. This study provided a mechanistic insight of drought stress tolerance in rice.