Through-silicon vias (TSVs) technology provides an effective approach for "more than Moore," however, the stress caused by TSVs may cause the surrounding devices to be squeezed and cause failure. In order to reduce the thermal stress of the TSV while innovatively considering the anisotropy of the silicon substrate, a shallow trench isolation (STI) structure was designed, and the influence of the shape and size of the STI on the stress reduction effect was studied. The research results show that the petal-shaped STI structure reduces the thermal stress caused by TSV by 26% and the KOZ area by 31%, which provides a solution for reducing the stress and KOZ area in the anisotropic silicon substrate.