The instant disclosure provides an intelligent CAA (Critical Area Analysis) failure pre-diagnosis system and method for a design layout. The intelligent CAA failure pre-diagnosis method includes the steps of obtaining a design layout of an object and defining at least one layout region having a layout pattern thereon, obtaining a plurality of defects, comparing the defects one-by-one to a predetermined portion of the layout pattern in the order of their sizes, and calculating a CAA failure risk level of the layout region according to the comparison result.