Fault trip of overload line transfers the power flow to other lines in the associated transmission section, which results in interlocking tripping accident. The key to prevent cascading tripping accidents is to quickly formulate a reasonable and effective power flow control strategy to eliminate line overload. In view of the defects of low accuracy of sensitivity method and too much calculation of optimization method, a double-layer optimal power flow control strategy of transmission section based on positive and negative comprehensive sensitivity is proposed. Considering the overall regulation effect of nodes on overload and heavy load line power flow, the positive and negative comprehensive sensitivity index is proposed, and then the power flow control strategy is quickly formulated by double-layer optimization method. In order to prevent the surge of computation caused by too large search space, a multi-objective selecting optimization model of the first layer scheduling nodes is established to optimize the scheduling nodes involved in the adjustment. On this basis, the second layer power flow regulation optimization model is constructed to obtain the accurate output adjustment of the scheduling nodes. The above model realizes the accurate dispatching of power flow out of limit on the transmission section. The simulation results of IEEE 39-bus system and a provincial power grid verify the rapidity and accuracy of the proposed method.