Drought stress, especially during the seedling stage, seriously limits the growth and development of maize. Understanding the response of maize to drought is the first step in the breeding of tolerant genotypes. Recent advances in deep-sequencing and proteomic techniques, such as isobaric tags for relative and absolute quantitation (iTRAQ), can provide large-scale comparisons and reliable quantitative measurements. Despite previous studies on drought resistance mechanisms by which maize cope with water deficient, the link between physiological and molecular variations are largely unknown. Therefore, understanding the drought tolerance mechanisms of different maize varieties is essential for genetic manipulation and/or cross breeding in maize. Towards this goal, we used a comparative physiological and proteomics analysis approach to monitor the changes of two different drought-resistant maize varieties.