Aims <p>The contradiction matrix in the field of general engineering was introduced into the field of drug safety governance, and the contradiction matrix in the refinement of drug safety governance was constructed to provide innovative ideas for solving the problem of drug safety governance, so as to promote the refinement of drug safety governance and ensure the safety of drug use.</p> Methods <p>Firstly, the problems of different governance subjects in drug safety governance were sorted out from the perspective of co-governance by multiple subjects. Secondly, the problem was parameterized, and the sorted problems were transformed into corresponding parameters for representation, and 18 parameters for refinement of drug safety governance were obtained. Thirdly, the contradiction matrix in the refinement of drug safety governance was constructed by combining 40 innovative principles. Finally, the practical application steps and application effects of the contradiction parameters and the contradiction matrix were discussed through case analysis.</p> Results <p>The results show that the constructed parameters in the refinement of drug safety governance can better represent the problem attributes existing in drug safety governance, and the constructed contradiction matrix can provide innovative ideas for drug safety governance.</p> Conclusion <p>The contradiction matrix can be used to analyze the problems existing in the refinement of drug safety management preferably, and match the specific problems with management parameters. The conflict matrix constructed and 40 invention principles are used to solve practical problems, so as to provide decision-making help and innovative ideas to solve problems for drug safety governance.</p>