Lonicera confusa was a medical plant which could adapt to the Ca-rich environment in the karst area of China. The photosynthesis, relative chlorophyll content,differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) of L. confusa that cultivated in calcareous and sandstone soils were investigated. The results showed that the relative chlorophyll content and net photosynthesis rate of L. confusa in calcareous soil are much higher than that planted in sandstone soil, the higher content of calcium might play a role in keeping the chloroplast from harm and showed higher photosynthesis rate. The transpiration and stomata conductance were decreased in calcareous soil, which might result from the closure of stomata. The GeneFishing and proteomic results showed that the expression of DEGs and DEPs were critical for photosynthesis and stomata closure, such as RuBisCO, photosynthetic electron transfer c and malate dehydrogenase varied in the leaves of L. confusa that cultivated in different soils. These DEGs or DEPs were further found to be directly or indirectly regulated by calcium sensor proteins. This study enriched our knowledge of the molecular mechanism of high net photosynthesis rate and lower transpiration of L. confusa that cultivated in the calcareous soil in some degree.