Degradation of ciprofloxacin (CIP) in water by photocatalysis using metal-free carbon nitride (CN) is an effective route. Here, we rationally adopt a “kill two birds with one stone” strategy to prepare N-vacancy (V_N) and O-doping co-modified CN (V_N-OCN_2.0) by a one-pot sintering process, wherein surface atomic microenvironment is judiciously reconfigured. V_N-OCN_2.0 accomplishes 100 % CIP removal within 12 min with a 69.5-fold higher pseudo-first-order kinetic constant than CN. Furthermore, V_N-OCN_2.0 generates an ultra-high concentration of reactive oxygen species (ROSs), which is 113.4 times higher than CN. Such excellent activity is attributed to a synergistic effect of V_N as electron-rich centers and O-doping as reaction active centers. Simultaneously, V_N-OCN_2.0 integrated sodium alginate hydrogel (V_N-OCN_2.0/SAG) can remove 100 % CIP without decay after 20 cycles. In addition, photodegradation pathways and biotoxicity are investigated by HPLC-MS, quantitative mathematical modeling of conformational relationships, and in vitro E. coli culture experiments. This study enriches a precise rearrangement of surface atoms, elucidates its collaborative functions in facilitating the efficient generation of ROSs and profound mineralization of antibiotics, and integrates SAG to tackle engineering challenges related to secondary pollution and intricate recycling of powder catalysts.