Optical diffuse spectroscopy is crucial in non-invasive measurements and quick analysis of biological tissues. However, the lack of exact analytical solution limits its application. In this paper, a semi-empirical formula for diffuse reflectance is elaborated on the basis of the photon migration theory and the second-order similarity relation, and the influence of second-order parameter γ on the semi-empirical formula is studied by use of Monte Carlo method. Results show that the diffuse reflectance changes with γ nonlinearly when a small aperture detector is used to collected diffuse light. Finally, the proposed semi-empirical formula is mathematically simple compared with the other theoretical mode used at present, and offers a new theoretical and technical support in the measurement of the tissue optical parameters and the application of diffuse reflectance spectroscopy.