Heat-integrated distillation is an improved distillation technique with remarkable energy-saving potential. A control scheme with a variable sensitive stage temperature set-point is proposed to solve the control problem of a heat-integrated distillation column (HIDiC). An online estimator is designed to support the variation of the set-point. The locations of the stage temperature measurements are carefully selected based on a combination strategy with three steps. First, the sensitive stages are selected. Then, the following stages are determined by a PCA-based method. Finally, a maximum differentiation method provides the remaining measurement selections. According to the profile parameters estimated by the proposed estimator, the set-point of the sensitive stage temperature is adjusted adaptively to reduce the influence of the disturbances. Two commonly-used PID controllers, the sensitive temperature control and the temperature differential control, are developed as the comparative study. The simulation results show that the proposed control scheme has a distinct advantage in restraining different disturbances.