In order to evaluate the influence of intermediate principal stress and major principal stress direction on the drainage-induced deformation of natural soft clay, a series of drained directional shear tests is carried out on Wenzhou natural soft clay with different intermediate principal stress coefficients and different major principal stress directional angles, using a GDS hollow cylinder torsional shear apparatus. During the tests, the shear stress is increased gradually until the specimens failed, while the major principal stress direction and the intermediate principal stress coefficient remain unchanged. The influences of intermediate principal stress coefficient and major principal stress direction are discussed on the relationship between the deviator stress and major principal strain, and the relationships between the major principal strain and the intermediate principal strain, minor principal strain and volumetric strain. It is found that the anisotropy expressed by the stress-strain relationship is affected by different intermediate principal stress coefficient and major principal stress direction. When the intermediate principal stress coefficient remains as 0.00 and 1.00, the influence of major principal stress direction on stress-strain relationship is insignificant. However, when the intermediate principal stress coefficient reaches 0.50, the secant modulus in stress-strain relationship is significantly influenced by major principal stress direction. When the major principal stress direction angle is 30°, the intermediate principal strain changes from compressive state to tensile state as the intermediate principal stress coefficient increase from 0.00 to 0.50. When the major principal stress direction angle is 45°, the intermediate principal strain changes from compressive state to tensile state when the intermediate principal stress coefficient increases from 0.00 to 1.00.