Helicobacter pylori, an etiological agent of gastroduodenal diseases, undergoes drastic morphological transition from spiral shape to coccoid form under oxidative stress. However, the knowledge of the specific expression profile in response to oxidative stress is relatively limited. Here, we report global proteomic analysis of H. pylori coccoids under oxidative stress. Two-dimensional gel electrophoresis analysis of H. pylori featuring coccoid revealed that 10 unique protein spots exhibit different expression profiles with comparison of that under normal microaerophilic condition. In total, seven proteins including superoxide dismutase, alkyl hydroperoxide reductase, urease G, and so forth were confirmed using matrix-assisted laser desorption/ionization time-of-flight/mass spectroscopy and then validated by reverse transcription-polymerase chain reaction, indicating that they play key roles in the physiological adaptation mechanisms of H. pylori to oxygen challenge. These data provide preliminary insights into H. pylori on coccoid generation under oxidative stress.