Aims The aim of the study was to investigate the proteomic changes and antioxidant enzyme activity in chromium-resistant Bacillus cereus VITSH1 in response to heavy metal toxicity. Methods and Results The variation in protein expression and antioxidant enzyme activity in the presence and absence of metal was studied in B. cereus VITSH1. The differentially expressed proteins in chromium-treated conditions were determined by SDS PAGE. The proteins involved in metal binding, protein biosynthesis, protein folding, energy metabolism and motility were identified by mass spectrometry coupled with bioinformatics search tools. The in gel assays for antioxidant enzymes indicated a change in their activity under metal stress conditions. Conclusions The findings of this study suggest that the organism combats metal stress probably by restricting the entry of metal inside the cell. The role of the differentially expressed proteins clearly indicates that the first line of defence is to avoid the entry of metal into the cell either by possessing a modified outer membrane or by moving away from the toxicant. Further work on the identification of other proteins playing a role in resistance would help in integrating the available knowledge on the resistance mechanisms the organisms employ to combat toxicity. Significance and Impact of the Study The proteomic changes in the metal-exposed bacteria would give an insight into the proteins involved in metal resistance mechanisms and thereby aid in the development of biosensor-based technology for heavy metal detection.