Fault diagnosis plays an important role in complicated industrial process. It is a challenging task to detect, identify and locate faults quickly and accurately for large-scale process system. To solve the problem, a novel MultiBoost-based integrated ENN (extension neural network) fault diagnosis method is proposed. Fault data of complicated chemical process have some difficult-to-handle characteristics, such as high-dimension, non-linear and non-Gaussian distribution, so we use margin discriminant projection(MDP) algorithm to reduce dimensions and extract main features. Then, the affinity propagation (AP) clustering method is used to select core data and boundary data as training samples to reduce memory consumption and shorten leing time. Afterwards, an integrated ENN classifier based on MultiBoost strategy is constructed to identify fault types. The artificial data sets are tested to verify the effectiveness of the proposed method and make a detailed sensitivity analysis for the key parameters. Finally, a real industrial system—Tennessee Eastman (TE) process is employed to evaluate the performance of the proposed method. And the results show that the proposed method is efficient and capable to diagnose various types of faults in complicated chemical process.