Although nanozyme has become an emerging area of research attracting extensive attention recently, the activity and specificity of currently reported nanozymes are generally lower than those of natural enzymes. Developing highly active and specific nanozymes is therefore extremely necessary and also remains a great challenge. Superoxide dismutase (SOD) catalyzes the disproportionation of cytotoxic O2·− into hydrogen peroxide and oxygen, and plays an important role in reducing human oxidative stress. In this work, we prepare Cu single-atom catalysts (Cu/GO SACs, GO = graphene oxide) through a simple and low-cost strategy at room temperature using Cu foam and graphene oxide. Cu/GO SACs can maintain excellent catalytic activity under harsh environment. Compared with the natural enzyme, SOD-like Cu/GO SAC nanozyme has higher catalytic activity and meanwhile, it does not possess the common properties of other mimic enzymes often existing in nanomaterials. Based on the excellent SOD-like enzyme activity of Cu/GO SACs, it successfully eliminates the active oxygen in cigarette smoke. This work not only provides a new idea for the design and synthesis of nanozymes with excellent SOD mimetic properties, but also is promising in the treatment of lung injury and inflammatory diseases related to free radical production.