This article concerns with the regulation and fault-tolerant control of non-minimum phase nonlinear processes with mismatched uncertainties. A variable structure controller, switching between a first-order sliding mode control and a second-order sliding mode control, is proposed to regulate the output and to stabilize the unstable zero dynamics with mismatched uncertainties. Once detected, the fault is estimated on-line by an approximator of radial basis function network; the control law is reconfigured to compensate the fault with closed-loop system asymptotically stable. The application of the proposed algorithm to a non-minimum phase continuously stirred tank reactor (CSTR) is illustrated in the presence of matched and mismatched uncertainties and component fault. (C) 2006 Elsevier Ltd. All rights reserved.