The invention discloses a large-sized internal supercharging shaft sealing device. An M type expansion sealing part is installed at an end sealing position of a rotary shaft; a U type sealing protection bush sleeves the M type expansion sealing part; the M type expansion sealing part is made of elastic materials; threaded air inlet pipes are installed on lateral walls of the M type expansion sealing part and the U type sealing protection bush; a compressed air source is communicated with the exterior of the threaded air inlet pipes; a press plate is arranged at the external end of the U type sealing protection bush in a pressing mode. The large-sized internal supercharging shaft sealing device thoroughly solves leakage caused by abrasion due to eccentricity of the shaft, is particularly suitable to a large-sized shaft, wide in applicable range, simple in installation and free of maintenance and achieves low cost and high efficiency.