The main purpose of this paper is to design a self-tuning control algorithm for an adaptive cruise control (ACC) system that can adapt its behaviour to variations of vehicle dynamics and uncertain road grade. To this aim, short-time linear quadratic form (STLQF) estimation technique is developed so as to track simultaneously the trend of the time-varying parameters of vehicle longitudinal dynamics with a small delay. These parameters are vehicle mass, road grade and aerodynamic drag-area coefficient. Next, the values of estimated parameters are used to tune the throttle and brake control inputs and to regulate the throttle/brake switching logic that governs the throttle and brake switching. The performance of the designed STLQF-based self-tuning control (STLQF-STC) algorithm for ACC system is compared with the conventional method based on fixed control structure regarding the speed/distance tracking control modes. Simulation results show that the proposed control algorithm improves the performance of throttle and brake controllers, providing more comfort while travelling, enhancing driving safety and giving a satisfactory performance in the presence of different payloads and road grade variations.