An antibacterial Ag nanocluster-based hydrogel (Ag NC@BC) is prepared by the in situ formation of Ag NCs on the nanofibers of a natural bacterial-cellulose (BC) hydrogel. The Ag NC@BC exhibits superior, broad-spectrum antimicrobial performance against both Gram-positive and Gram-negative bacteria, and has a long-acting bactericidal efficacy compared to pristine Ag NCs due to its controlled-release feature for Ag species. Moreover, this fabricated hydrogel also possesses excellent biocompatibility. All of these advantages of Ag NC@BC endow it with great potentials in battling bacterial infections.