The present disclosure provides a system and a method for quickly diagnosing, classifying, and sampling in-line defects based on a CAA pre-diagnosis database. The method includes the steps of obtaining a design layout of an object and a defect data of an important process stage of the object, obtaining a pre-diagnosis data group related to the design layout from a CAA pre-diagnosing database, and judging a killer defect index and a failure risk level of the defect data according to the pre-diagnosis data group.