This paper researches the feature description and automatic signature generation algorithm of polymorphic worms. It proposes a new signature generation approach for polymorphic worms-MS-PADS (multiple separated string position-aware distribution signature), which integrate the advantage of PADS and Polygraph. It solved the problem of PADS signature width determination under strong background noise conditions. This method could generate high quality signatures of polymorphic worms with low false-positive rate and high detection precision rate.