Given that human factors are the key factors that affect flight safety, and the decision-making factors are difficult to measure, so the SHELL model and the matter element theory were combined to carry out the study of flight safety comprehensive assessment. Based on the SHELL model, the flight safety assessment index system is established by the human factors of the aircrew as the main object. The weights of each index in the evaluation index system are calculated by using the analytic hierarchy process (AHP). The evaluation model was established by the matter element theory to calculate the correlation degree of evaluation index for each security level, and then the comprehensive evaluation result of flight safety assessment is calculated. Through further analysis of the results, the key factors influencing flight safety can be found in order that airlines can take precautions in advance accordingly, safety management can be strengthened and the occurrence of flight accidents can be avoided. At the end of the article, an example verifies that the method is feasible and valid, and the uncertainty of the assessment process can be solved to the maximum extent. It provides a feasible method for flight safety management of airlines.