Regulation of hypnosis level on bi‐spectral index monitor (BIS) during a surgical procedure in propofol anaesthesia administration is a challenging task for an anaesthesiologist in multi‐tasking environment of the operation theater. Automation in anaesthesia has the potential to solve issues arising from manual administration. Automation in anaesthesia is based on developing the three‐compartmental model including pharmacokinetics and pharmacodynamic of the silico patients. This study focuses on regulation of the hypnosis level in the presence of surgical stimulus including skin incision, surgical diathermy and laryngoscopy as well as inter‐patient variability by designing super‐twisting sliding mode control (STSMC). The depth of the hypnosis level is maintained to 50 on the BIS level in the maintenance phase after improving the induction phase to 60 s using the conventional sliding mode control and 30 s with STSMC. The proposed scheme also compensates the inter‐patient variability dynamics including height, age and weight of the different silico patients. Moreover, the surgical stimuli direct the hypnosis level towards the state of consciousness and stimulate the controller to provide continuous drug infusion during the interval 80–90 s. Simulation results witness that the oscillatory behaviour is observed in drug infusion to ensure the moderate level of hypnosis (40–60) for general surgery.