Nanozymes are promising alternatives to natural enzymes, but their use remains limited owing to poor specificity. For example, CeO 2 activates H 2 O 2 and displays peroxidase (POD)-like, catalase (CAT)-like, and haloperoxidase (HPO)-like activities. Since they unavoidably compete for H 2 O 2 , affecting its utilization in the target application, the precise manipulation of reaction specificity is thus imperative. Herein, we showed that one can simply achieve this by manipulating the H 2 O 2 activation pathway on pristine CeO 2 in well-defined shapes. This is because the coordination and electronic structures of Ce sites vary with CeO 2 surfaces, wherein the (100) and (111) surfaces display nearly 100% specificity toward POD-/CAT-like and HPO-like activities, respectively. The antibacterial results suggest that the latter surface can well-utilize H 2 O 2 to kill bacteria (cf., the former), which is promising for anti-biofouling applications. This work provides atomic insights into the synthesis of nanozymes with improved activity, reaction specificity, and H 2 O 2 utilization. KEYWORDS: nanozymes, CeO 2 , coordination/electronic structure, H 2 O 2 activation pathway, H 2 O 2 -associated enzymatic reactions