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Runway incursion is the safety management core of civil airports, and the influencing factor of runway incursion is a hot topic in the practical and academic circles. To identify key influencing factors and determine interaction ways, typical runway incursions were analyzed using the software-hardware-environment-liveware model (SHELL). Fifteen influencing factors were identified and extracted. The centrality and cause of influencing factors were calculated by decision-making trial and evaluation laboratory (DEMATEL) and interpretative structural modelling (ISM). A multi-layer interpretative structural model was constructed for layering of influencing factors. Results indicate that inadequate attention of airport leaders to safety is the root factor. System formulation and educational training are deep influencing factors. Oversight and the operation error rate of ground officials are direct influencing factors. Runway incursion could be fundamentally controlled and prevented by improving the root factor. The proposed DEMATEL-ISM method can analyze the influencing factors of runway incursions and their influencing mechanism, thereby offsetting the shortcomings of the linear risk factor statistical model and offering a novel decision-making idea and approach for runway incursion control.