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.