The inverter system is a typical hybrid system consisting of an inverter, a filter, a load, and a controller. The traditional modeling method cannot effectively reveal the state characteristics of the system, affecting the accuracy of fault analysis and diagnosis of the power switching device. This paper presents a new model-based fault diagnosis approach for the open-circuit fault of neutral-point clamped (NPC) three-level inverter. Firstly, the working mechanism of the three-level inverter is analyzed, a three-level inverter mixed logic dynamic(MLD) model is built by analyzing hybrid system theory and modeling methods. Based on the MLD model, the state estimator of the inverter in the non-faulty situation is constructed. Then, the residual equation is obtained by comparing the true value of the three-phase current generated by the inverter with the current estimate value of the three-phase current generated by the state estimator. Finally, the residual equations in different fault situations are analyzed to realize the open-circuit fault diagnosis of single-switch. In order to verify the effectiveness of the method, a simulation experiment was carried out. The experimental results show that the proposed method can quickly and accurately diagnose the single-switch open-circuit fault of the inverter。