A novel approach has been proved to quickly and non-invasively determine the optical properties of human skin in vivo. It is based on the diffuse reflectance approximation model and subjected to the well established library of absorption spectra of water and hemoglobin. Under the nonlinear least-square algorithm, fitting the measured spectra in the range of 400-1000 nm to the diffusion approximation model, the reduced scattering coefficient and absorption coefficient of skin tissue can be quickly determined in vivo. The results show that this method is convenient and suitable for the real-time clinical application.