Objective To explore the prone site of pressure injury in buttock in sitting position and the biomechanical response of different soft tissues, so as to provide reference for effective prevention of deep tissue pressure injury. Methods Based on CT scan data of the buttocks, a finite element model of the buttocks in sitting position was established, including bone, muscle, fat, skin tissue and cushion model. Tissue injury was simulated using life-death elements. The pressure measurement data of the experimental cushion interface were compared with the finite element simulation results to verify the validity of the model. To simulate the mechanical state of the sitting position, the stress and strain of the soft tissue were studied, and the compressive stress in different soft tissues and the possible damage after exceeding the limit value were analyzed. Results By comparing the simulation results of the cushion model with the experimental interface pressure measurement results, the model is proved to be effective. Stress concentration occurred in the soft tissue below the ischial tuberosity in the sitting position. The peak values of transverse compressive stress and shear stress in gluteus maximus were 38 kPa and 3.4 MPa; the maximum compressive stress and shear stress in adipose tissue did not appear directly below the ischial tuberosity, which were 22 kPa and 4.5 MPa. Conclusions Deep tissue injury may occur when soft tissue is subjected to a certain time and magnitude of pressure load. When the sitting position is maintained for a certain period of time, the position should be changed in time to reduce the probability of pressure injury. This study provides a biomechanical basis for the prevention of pressure injury, which has important clinical research value.