Listeria monocytogenes is a food-borne pathogen of significant threat to public health. High Hydrostatic Pressure (HHP) treatment can be used to control L. monocytogenes in food. The CtsR (class three stress gene repressor) protein negatively regulates the expression of class III heat shock genes. In a previous study, a spontaneous ctsR L. monocytogenes deletion mutant 2-1 that was able to survive under HHP treatment was identified; however, there is only limited information about the mechanisms of survival and adaptation of this mutant in response to high pressure. Microarray technology was used to monitor the gene expression profiles of ctsR mutant 2-1 under pressure treatments (450 Mpa, 3min). Some of the gene expression changes determined by microarray assays were confirmed by real-time RT-PCR analyses. Compared to non-pressure-treated ctsR mutant 2-1, 14 genes were induced (> 2-fold increase) in the ctsR deletion mutant whereas 219 genes were inhibited (< -2-fold decrease) by pressure treatments. The induced genes included genes encoding proteins involved in synthesis of purines, pyrimidines, nucleosides, and nucleotides, transport and binding, transcription, cell membrane, DNA and energy metabolism, protein synthesis, and unknown functions. The inhibited genes included genes encoding proteins for transport and binding, cell envelope, transcription, amino acid biosynthesis, regulatory functions, cellular processes and central intermediary metabolism. The information concerning L. monocytogenes survival under HHP at the molecular level may contribute to improved HHP treatments for food processing.