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Aiming at the fatigue and comfort issues of human-machine contact Interface in automobile driving and based on physiological and anatomical principle, the physiological and biochemical process of muscles and nerves in the formation and development of fatigue is analyzed systematically. The fatigue-causing physiological characteristic Indexes are mapped to biomechanical Indexes like muscle stress-strain, the compression deformation of Wood vessels and nerves etc.from the perspective of formation mechanism. The geometrical model of skeleton and parenchyma is established by applying CT-scanned body data and MRI images. The general rule of comfort body pressure distribution is acquired through the analysis of anatomical structure of buttocks and femoral region. The comprehensive lest platform for sitting comfort of 3D adjustable contact Interface is constructed. The lest of body pressure distribution of human-machine contact interface and its comparison with subjective evaluation indicates that the biomechanical Indexes of automobile driving human-machine contact interface and body pressure distribution rule studied can effectively evaluate the fatigue and comfort issues of human-machine contact interface and provide theoretical basis for the optimal design of human-machine contact interface.