This paper describes the design of a hybrid control for continuous stirred tank reactor (CSTR), with parameter uncertainty and system disturbance by intelligent techniques. CSTR is characterized by nonlinear and time-varying behaviour. Control of CSTR is a challenging problem. The proposed hybrid controller consists of a genetic algorithm (GA) based proportional integral derivative (PID) control and an internal model control (IMC). The IMC is constructed with a backpropagation (BPN) algorithm based neural emulator for the model and an Takagi Sugeno Fuzzy based inverse adaptive neuro-fuzzy inference system (ANFIS) as the controller. The IMC provides a very good tracking control and leads to control performance degradation in the case of regulatory problem which is solved using the GA-based PID control. GA-based PID implements the characteristics of GA’s global optimization to optimize the PID’s control parameters: Kp, Ki, Kd to provide best control effect. The proposed model provides an effective controllable range and gives robust control performance.