The exchange bias effect with anisotropy perpendicular to the device plane is promising for exploring the next generation of spintronics devices. However, the effective modulating of exchange bias remains challenging because the understanding of the mechanism on tuning the exchange bias anisotropy is lacking and worth investigation. In this study, epitaxial La0.7Sr0.3MnO3/NiO (LSMO/NiO) bilayers were deposited on the (001)-orientated SrTiO3 and MgO substrates by pulse laser deposition to further explore the mechanism behind the anisotropy of EB effect at the LSMO/NiO interface. The results demonstrate the exchange bias transition from in-plane to out-of-plane by changing the substrate from SrTiO3 to MgO. According to the strain analyses, the substrate strain-induced spin reorientation transition of NiO plays an important role on the exchange coupling at the LSMO/NiO interface, leading to the EB effect transition. The significance of the interaction between strain and spin at the heterointerface is revealed, which provides a possible way for the regulation of interfacial magnetism.