Carissa spinarum is one of the secondary advantage plants grown in dry-hot valleys in China, which can survive under stress conditions of high temperature and extreme low humidity. Here, we studied the physiological and proteomic changes of C. spinarum in response to 42 degrees C heat stress treatment in combination with drought stress. Dynamic changes in the leaf proteome were analyzed at four time points during the stress treatment and recovery stages. Approximately, 650 protein spots were reproducibly detected in each gel. Forty-nine spots changed their expression levels upon heat and drought treatment, and 30 proteins were identified by MS and 2-D Western blot. These proteins were classified into several categories including HSP, photosynthesis-related protein, RNA-processing protein and proteins involved in metabolism and energy production. The potential roles of these stress-responsive proteins are discussed.