In this paper, we address an NPN Boolean matching algorithm. The proposed structural difference signature (SDS) of a Boolean function significantly reduces the search space in the Boolean matching process. The paper analyses the size of the search space from three perspectives: the total number of possible transformations, the number of candidate transformations and the number of decompositions. We test the search space and run time on a large number of randomly generated circuits and Microelectronics Center of North Carolina (MCNC) benchmark circuits with 7–22 inputs. The experimental results show that the search space of Boolean matching is greatly reduced and the matching speed is obviously accelerated.