Nitric oxide (NO) is known as a typical air pollutant and can be extremely hazardous to humans and animals. The pursuit of highly efficient and selective sensing materials for NO detection is still an enormous challenge due to the technical hurdles. In this study, ZIF-8 derived ZnO hollow nanostructures loaded with dispersed Ag nanocrystals (NCs) were synthesized for the first time using a simple solution method. These nanostructures exhibit an excellent NO sensing performance at an operating temperature of 125 °C. The highest response value (66.6, 100 ppm), shortest response time (10 s), and best NO selectivity and stability were achieved when the loading amount of Ag NCs was 0.05 mL. Further experiments demonstrated that the electronic and chemical sensitization effect of the Ag NCs and the unique porous structure of ZIF-8 derived ZnO were mainly responsible for the improved sensing capability. These results indicate that the ZnO hollow nanostructures loaded with Ag NCs are promising sensing materials for NO detection, and this study presents an effective model for the modification of MOS-based gas sensing materials.