The deformation characteristics of rock mass and the coefficient of subgrade reaction are directly related to the internal force, final deformation and deformation uniformity of foundation. Determination of reasonable coefficient of subgrade reaction is important for high-rise buildings, especially super high-rise buildings. Taken a super-high-rise building in Chengdu as example, plate loading tests of red-bed soft rock foundation with different plate sizes and shapes were carried out. Besides, the uniaxial compressive strength test (UCS), conventional triaxial compression test and direct shear test of red-bed mudstone were carried out. Based on the results of laboratory and in-situ test, the relationship between UCS, elastic modulus, bearing plate size and coefficient of subgrade reaction were analyzed. The results show that the coefficient of subgrade reaction has a tendency to increase with UCS of rock, and the smaller the bearing plate size is, the more discrete test data will be obtained. The coefficient of subgrade reaction of red-bed mudstone obtained by 500 mm square bearing plate test is recommended. It is found that the coefficient of subgrade reaction of red-bed mudstone layer has a hyperbolic empirical relationship with the plate size. If the coefficient of subgrade reaction of red-bed mudstone layer is modified according to the empirical formula of clay or sand recommended by the code, it will cause a large error. Therefore, it is suggested that the coefficient of subgrade reaction is modified based on the hyperbolic empirical relationship.