In order to explore the mechanism of drought resistance of upland cotton varieties,we chose and used drought-resistant upland cotton（Gossypium hirsutum L.）variety,‘Zhong H177’ and drought-sensitive variety,‘Zhong S9612’ as materials.Different water stress-induced proteome changes in different cotton（G.hirsutum L.）leaves at tri-leaf stage of seedlings under drought stress were analyzed by two-dimensional gel electrophoresis combined with mass spectrometry analysis.The results indicated that there had a big difference of protein components in different cotton leaves under drought stress.There were total 30 differentially expressed proteins discovered in ‘Zhong H177’ under drought stress,while 47 differentially expressed proteins discovered in ‘Zhong S9612’,only 11 protein spots appeared in ‘Zhong H177’,28 protein spots in ‘Zhong S9612’,8 protein spots had consistent expression,but 11 protein spots didn’t.43 differentially expressed proteins were identified and confirmed by MALDI-TOF-TOF MS,Functional classification analysis indicated that drought induced proteins were involved in photosynthesis,material and energy metabolism,stress tolerance protein,solute translocation and active oxygen scavenging.The difference in Rubisco activase and ATP synthase involved in energy metabolism is the largest,which could lay a foundation preliminarily for the research of drought resistance mechanism in upland cotton.