A comparative analysis of drought and high temperature responsive proteins, which means to provide insight into the molecular mechanism of potato stress tolerance. In the presented study, two potato cultivars, differing in dehydration tolerance, were compared. An analysis of their morphological, physiological and root proteome related traits proved that, although water shortage, as well as high temperatures cause the dehydration of plants, the response to those stresses at the proteome level was significantly different. LC–MS/MS protein identification showed that in roots of the sensitive cultivar, in response to drought, most changes concern increased abundance of defence- and detoxification-related proteins, while in tolerant plants, significant changes in abundance of energy and carbohydrate metabolism related proteins were observed (data are available via ProteomeXchange with identifier PXD020259). Moreover, in response to high temperatures, in the sensitive cultivar, decreased abundance of proteins involved in cell energetic metabolism was detected, while in the tolerant cultivar, the majority of proteins from this group was abundant. It can be suggested that such comparative proteome analysis indicates the fine tuning metabolism as a major factor of stress tolerance of potato plants.