The attachment of microbial biomass on solid surfaces, also referred to as biofouling, is a universal phenomenon that occurs in natural and engineering systems. However, traditional antibiofouling surfaces based on either the release of biocidal compounds or surface chemical/physical design have some drawbacks, such as the high cost, the complicated process, the low accuracy, and the limitation to achieve coatings over large area. Herein, to overcome these problems, a superhydrophobic coating is fabricated via spraying the mixture of hydrophobized zinc oxide nanoparticles and epoxy resin. The zinc oxide nanoparticles form a multiscale roughness, and the epoxy resin promotes the robustness of the coating. The so-formed superhydrophobic coating resists the attachment of protein, bacteria, and marine algae. It is expected that the so-developed superhydrophobic coating can be applied in the fields of biomedical instruments, antimicrobial material, marine platform, and ships.