Abstract: Severe disease damage under hot and humid environment is the important factor which reduces the yield of pepper cultivated in open field and greenhouse in south of our country. In this study, the molecular mechanism for pepper response to high temperature and humidity and pathogen infection was studied, and the functions of CaWRKY40 transcription and regulation in pepper heat-tolerance, disease-resistance, and disease-resistance under high temperature and humidity condition had been summayized. On the above basis, the pepper varieties selection were established by ecological pressure selection, based on diseased nursery and high temperature and humidity treatment, combined with levels of CaWRKY40 transcription and expression. A series of new Minjiao pepper varieties were bred by selection on various pepper germplasm resources obtained by sexual hybridization and mutation, and all of them were highly resistant to diseases under hot and humid environment, which could be applied in south China in open and protected cultivation.