The heat-exchanger/reactor (HEX reactor) is a kind of plug-flow chemical reactor which combines high heat transfer ability with good chemical performances. It is designed under the popular trend of process intensification in chemical engineering. Previous researches have investigated its characteristics and developed its nominal model. This paper is concerned about its fault tolerant control (FTC) applications. To avoid the difficulties and nonlinearities of this HEX reactor under chemical reactions, a two-layer multiple model structure is proposed to designed its FTC scheme. The first layer focuses on representing the nonlinear system by a bank of local linear models while the second layer uses model banks for approaching faulty situations. Corresponding model predictive controller banks are designed according to each model bank which are achieved by system identification method to handle the FTC problem. Simulation results showed its validity in the fifth section. The idea of two-layer multiple model structure presents a general framework for FTC design of complex and highly nonlinear systems such as the HEX reactor whose mathematic model has been created. It implements the design process in an unusual way and could also be promoted to other cases.