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The safety, reliability and stability of air supply subsystems are still problems for the commercial applications of fuel cells; therefore, engine fault diagnosis and fault-tolerant control are essential to protect the fuel cell stack. In this study, a fault diagnosis and fault-tolerant control method based on artificial neural networks (ANNs) has been proposed. The offline ANN modification model was trained with a Levenberg–Marquardt (LM) algorithm based on other sensors' signals relevant to the current sensor of a 50 kW-grade fuel cell engine test bench. The output current was predicted via the ANN identification model according to other relevant sensors and compared with the sampled current sensor signal. The faults in the current sensor were detected immediately once the difference exceeded the given threshold value, and the invalid signals of the current sensor were substituted with the predictive output value of the ANN identification model. Finally, the reconstructed current sensor signals were sent back to a fuel cell controller unit (FCU) to adjust the air flow and rotate speeds of the air compressor. Experimental results show that the typical faults in the current sensor can be diagnosed and distinguished within 0.5 s when the threshold value is 15 A. The invalid signal of current sensor can be reconstructed within 0.1 s. Which ensures that the air compressor operate normally and avoids oxygen starvation. The proposed method can protect the fuel cell stack and enhance the fault-tolerant performance of air supply subsystem used in the fuel cell engine, and it is promising to be utilized in the fault diagnosis and fault-tolerant control of various fuel cell engines and multiple sensor systems.