Drought is a major constraint for wheat production that is receiving increased atten-tion due to global climate change. This study conducted isobaric tags for relative andabsolute quantitation proteomic analysis on near-isogenic lines to shed light on theunderlying mechanism ofqDSI.4B.1quantitative trait loci (QTL) on the short arm ofchromosome 4B conferring drought tolerance in wheat. Comparing tolerant with sus-ceptible isolines, 41 differentially expressed proteins were identified to be responsiblefor drought tolerance with ap-value of<0.05 and fold change>1.3 or<0.7. Theseproteins were mainly enriched in hydrogen peroxide metabolic activity, reactive oxy-gen species metabolic activity, photosynthetic activity, intracellular protein transport,cellular macromolecule localization, and response to oxidative stress. Prediction ofprotein interactions and pathways analysis revealed the interaction between transcrip-tion, translation, protein export, photosynthesis, and carbohydrate metabolism as themost important pathways responsible for drought tolerance. The five proteins, includ-ing 30S ribosomal protein S15, SRP54 domain-containing protein, auxin-repressed.