Alvinella pompejana is one of the most emblematic species of the animal communities colonizing the deep-sea hydrothermal vents of the East Pacific Rise. This extreme environment is characterized by high temporal variability of its physical–chemical parameters. Among these, the variation in concentration of available oxygen should lead to a specific physiological adaptive response of the animal. To evaluate the mechanisms of this response at a molecular level, a classical 2-DE-based proteomic approach has been implemented. After collection (Garrett-18S and -17S vent sites) animals were reconditioned in a high-pressure chamber pressurized at 260?bar and then the oxygen concentration was regulated to a constant value corresponding to hypoxia, normoxia or hyperoxia for 7?h. The soluble proteins from gills were then analyzed by 2-DE. The protein content of spots showing specific changes following oxygen concentration variation was determined based on comparison of MS/MS sequence data with a recently established A. pompejana ESTs database. Fifteen proteins, belonging mainly to three families, cytoskeleton protein, enzymes of energetic metabolism and heat shock proteins, have been identified as potentially involved in the response to the change in oxygen concentration. The significance of the relatively small set of proteins modulated by oxygen variations is discussed in the context of a potential universal cellular response to stress.