Under the condition of heavy rainfall, the rock and soil saturation of fully weathered granite slope increases, and the shear strength decreases, which is easy to cause slope instability. In this process, the change of matrix suction is the key factor leading to the change of shear strength. Taking Laoshan fully weathered granite slope in Qingdao as the research object, the soil and water characteristic curve (SWCC) of fully weathered granite based on Van Genuchten model was obtained by means of centrifuge test, undrained direct shear test, X-ray diffraction analysis, conventional silicate chemical total analysis test and scanning electron microscope test. The effect of matrix suction on the shear strength of fully weathered granite was studied systematically. The results show these as follows. The saturation of fully weathered granite soil is negatively correlated with matrix suction, and the soil samples with uneven gradation have stronger drainage capacity. The shear strength index is affected by matrix suction differently. Cohesion is more sensitive to the change of matrix suction than the angle of internal friction. There is a positive correlation between matrix suction and shear strength in fully weathered granite soil. The research results can provide theoretical guidance for slope prevention in fully weathered granite area.