Medical linear accelerators (MLAs) are critical components for radiation therapy, providing a state-of-the-art treatment platform for cancer therapy. The vacuum system is one of the most important MLA subsystems and its stable operation is necessary to generate high-quality beams. For vacuum system pressure control, traditional proportional-integral-derivative (PID) strategies have disadvantages such as inaccurate and imprecise control response due to its simple calculation. This paper presents an innovative adaptive integral sliding mode control (AISMC) strategy aimed at enhancing the response time, precision of control, and capability to reduce disturbances within the MLA vacuum system. In addition, a nonlinear MLA vacuum system mathematical model is established based on mechanism method. Stability of the developed vacuum control system is validated using Lyapunov stability theory. Simulation results illustrate that the proposed AISMC strategy has better response speed and accuracy than traditional PID-based systems, achieving better pressure tracking performance than traditional sliding mode control strategy with PID control. Most important for the proposed controller, system chattering is effectively mitigated.