An apparatus and method for searching for a protein active site by using a bottom-hat transformation are provided. First, an image of protein surface is generated and then a volumetric image is generated by sampling the protein surface in units of a predetermined length. Thereafter a morphology process is performed on the volumetric image, thereby extracting the protein active site from the morphology-processed volumetric image. Accordingly, it is possible to rapidly search for a protein active site in a 3D structural space.