This paper aims to solve the problem of optimal design on a comfortable human-machine arrangement of car drivers with different physical signs under dynamic manipulation. Based on the biomechanical characteristic of human skeletal muscle and Hill muscle mechanics model, this paper constructs the human seat musculoskeletal model of 5th, 50th, and 95th percentile physical signs of Chinese car drivers under dynamic manipulation. The six-degree-of-freedom flexible test bench was set up and the center composite method was used to optimize the number of experiments. The consistency and relevance analysis of the actual measurement and dynamic manipulation simulation was carried out to comprehensively analyze the human-machine arrangement parameters such as vehicle seat, pedal, and steering wheel, so as to realize the optimization design of the hard point size of comfortable driving posture and verify the rationality and applicability of the test results through the vehicle road test.