Considering comprehensively the influence of the relay protection, node voltage offset, geographical location and other factors, this paper puts forward a more accurate method based on the running state of power grid and topological structure of network to identify the vulnerable lines in power grid — the comprehensive betweenness method. Among them, the run-time state of grid is presented by power transmission of grid side and load side, the real-time power flow and flow margin. Combined with the number of generators which have exerted some influence on the grid with the number of load absorbing power from line, and taking line betweenness into account, the network topology structure can be analyzed. Taking IEEE39 system as the research object, the paper uses three kinds of chain attack to simulate when obtaining the order of vulnerable lines. Then the situation of the percentage of power transmission changing is used to analyze the effectiveness of the proposed comprehensive betweenness. The results show that the comprehensive betweenness proposed have a better recognition on vulnerable lines.