Deterioration of skin barrier function causes symptoms such as allergies because it allows various chemical substances to enter the human body. Quantitative evaluation of the thickness and water content of the stratum corneum is useful as a measure of skin barrier function in fields such as dermatology, nursing science, and cosmetics development. The stratum corneum is responsible for most of the skin barrier function, and this function has conventionally been evaluated using transepidermal water loss (TEWL). In this paper, we propose a new model for estimation of TEWL from measurements of the thickness of the stratum corneum and water content of the surface of the stratum corneum, and discuss the results of the measurements. By measuring the thickness and water content of the stratum corneum using confocal laser microscopy and confocal Raman spectroscopy, respectively, and examining the relationship of these variables with TEWL, we established a new potential model for estimating TEWL from these two variables. The correlation coefficient of the validation data was 0.886 and the root mean squared error was 8.18 points. These findings indicate the feasibility of qualitative evaluation of TEWL by measuring the thickness and water content of the stratum corneum.