H. salinarum cells exposed to IR showed a high level of oxidative damage to DNA and proteins. In contrast, exposure to hydrogen peroxide and superoxide - to the same level of survival - produced significantly less oxidative damage, indicating that cell death from chemical oxidants might be the result of interference with major metabolic pathways. We found that ROS scavenging enzymes essential for survival to hydrogen peroxide and superoxide were not necessary for H. salinarum survival to IR. Enzyme-free cellular extracts from H. salinarum showed high level of protection for protein activity against IR. Biochemical analysis of the enzyme-free extracts revealed essential roles in ROS scavenging for specific nucleosides, MnPO4 complexes, the accumulation of free amino acids and peptides, and high intracellular halides. This work contributed novel findings on the critical role played by non-enzymatic systems in IR resistance in H. salinarum and underlines the diversity of mechanisms that exists in response to environmental stresses.