Direct optical detection and imaging of single nanoparticles on a substrate in wide field underpin vast applications across different research fields. However, speckles originating from the unavoidable random surface undulations of the substrate ultimately limit the size of the decipherable nanoparticles by the current optical techniques, including the ultrasensitive interferometric scattering microscopy (iSCAT). Here, we report a defocus-integration iSCAT to suppress the speckle noise and to enhance the detection and imaging of single nanoparticles on an ultra-flat glass substrate and a silicon wafer. In particular, we discover distinct symmetry properties of the scattering phase between the nanoparticle and the surface undulations that cause the speckles. Consequently, we develop the defocus-integration technique to suppress the speckles. We experimentally achieve an enhancement of the signal-to-noise ratio by 6.9 dB for the nanoparticle detection. We demonstrate that the technique is generally applicable for nanoparticles of various materials and for both low and high refractive index substrates.