Air nanobubbles (A-NBs) in a circulating cooling water system have not been investigated, although their role is significant. In this paper, the influences of the contents of main salts and other parameters on the physicochemical characteristics and scale inhibition performance of A-NBs in circulating cooling water were investigated and the scale inhibition mechanism of A-NBs in a simulated circulating cooling water system was explored. A-NBs realized a higher scale inhibition rate of 90%, which was higher than that of 1-hydroxyethane-1,1-diphosphonic acid (40%), and A-NBs stably existed for more than 5 days in the complex water environment. Four interface functions were proposed to interpret the scale inhibition effect of A-NBs in circulating cooling water as follows. First, the negatively charged surface of A-NBs adsorbed cations (Ca 2+ ) reduced the concentration of scaling ions. Second, the negatively charged surface of A-NBs could also adsorb microcrystals, and their crystal-like seed action was conducive to the formation of large-size crystals, broke the rules of crystal growth, and reduced the adhesion of scales to the pipe wall. Third, A-NBs could also form a bubble layer after they were adsorbed on the inner surface of pipes, thereby preventing the deposition of scales on the surface. Fourth, A-NB burst caused local turbulence, increased the shear force onto the pipe surface, and reduced the scales adhering to the pipe surface. The interface effect of A-NBs in metal pipes is important in many industrial applications. This study laid the basis for the development of a new green A-NB scale-inhibiting technology.