Publisher Summary This chapter discusses adaptive nonlinear control algorithm based on the use of Hammerstein model, which was applied to keep the bioreactor temperature at the desired value. The sort of control algorithm is known as a nonlinear form of generalized predictive control (NLGPC). This control system is a flexible linear form of generalized predictive control (GPC), and it deals effectively with a range of nonlinear system. Third-order Hammerstein model was used to describe the dynamic behavior of the system. This model gives the polynomial relation between the reactor heat input and inlet temperature. In nonlinear GPC algorithm, the one-step Newton–Raphson root solution method was used, and the parameters of Hammerstein model were calculated online in every sampling time step. Successful application of NLGPC based on Hammerstein model was realized to control the bioreactor temperature. The performance of NLGPC was compared with GPC algorithm. The feasibility of NLGPC was tested by means of several experimental studies.