Terahertz time-domain spectroscopy (THz-TDS) has been applied in the detection of skin cancer, skin burn, scar treatment, and the THz spectral parameters in the time domain and frequency domain are used to discriminate the different tissues. In the general reflection THz in vivo measurement, the skin should be placed on the top surface of a medium window, resulting in water content change in skin surface because of occlusion, and finally, interfere the accuracy of the measurement. THz biomedical application is transferring from ex vivo to in vivo, the THz spectral parameters changing should be analyzed when measuring the occluded skin. In this paper, the occlusion process is measured using THz reflection system, and 13 feature parameters of measured THz signals such as peak to a peak value and Full width at half maximum (FWHM) are proposed and analyzed. Results show that the peak to the peak value of time-domain signals and transfer function and fitting slope of maximum and minimum value decay exponentially over occluding time while fitting slope and time distance of maximum and minimum value of transfer function increase exponentially over occluding time. The FWHM and log spectrum remain stable along with the occluding time. Afterwards, the double Debye model is used to describe the dielectric constant of skin in 0.2~1 THz frequency, and the combined genetic algorithm and Levenberg-Marquardt optimization method are used to extract the Debye parameters at a different occluding time. Results show that ε∞ and εs both increase exponentially with an increase of 27.8% and 12.5% respectively in 5 minutes, while the ε2, τ1 and τ2 remain stable over the occluding time. Next, the skin is taken regard as a stratified medium, based on the Bruggeman effective medium theory, the previous optimization algorithm which takes the measured reflectivity and calculated reflectivity as the objective function is also used to extract the skin water content along with occluding time. Results show that water content in stratum corneum grows exponentially with occluding time and increases by 23.8% in 5 minutes. Consequently, the THz spectral change results from occlusion of the skin due to the contact of the medium window should be carefully considered when applying the THz-TDs in clinical application. Our research could improve the accuracy of THz in vivo detection and promote its clinical application.