Abstract The problem of graph similarity measurement is fundamental in both complex networks and bioinformatics researches. Gene regulatory networks (GRNs) describe the interactions between the molecules in organisms, and are widely studied in the fields of medical AI. By measuring the similarity between GRNs, significant information can be obtained to assist the applications like gene functions prediction, drug development and medical diagnosis. Most of the existing similarity measurements have been focusing on the graph isomorphisms and are usually NP-hard problems. Thus, they are not suitable for applications in biology and clinical research due to the complexity and largescale features of real-world GRNs. In this paper, a fast similarity measurement method called FSM for GRNs is proposed. Unlike the conventional measurements, it pays more attention to the differences between those influential genes. For the convenience and reliability, a new index defined as influence power is adopted to describe the influential genes which have greater position in a GRN. FSM was applied in nine datasets of various scales and is compared with state-of-art methods. The results demonstrated that it ran significantly faster than other methods without sacrificing measurement performance