The use of protective clothing under extreme conditions leads to heat stress with undesired consequences on human physiology. As a prevention measure, thermal indices and thermophysiological models have been developed. Based on these models and indices, it is possible to estimate the time limits for staying under risky conditions, e.g., by the predicted rectal temperature whose value is one of the most important parameters used for assessing the heat stress. This article is focused on the comparison of rectal and mean skin temperature prediction realized by the Fiala-based thermophysiological model (FMTK) and Predicted heat strain (PHS) index with results from the real experiment for normal and protective clothing. Three types of ensembles were tested and simulated as follows: Klimatex underwear, air-permeable military NBC suit M2000 (FOP), and impermeable chemical protective clothing Tychem-F. The real experiments of thermal strain were performed with one male participant (80 kg, 1.75 m) walking on the treadmill located in the climate chamber. The temperature range for neutral and hot tests was set from 25 °C to 40 °C. The rectal temperature, skin temperatures, and heart rate were measured. The results showed that PHS index is well usable for normal clothing (Klimatex underwear) and air-permeable protective clothing (FOP) under various ambient temperatures, and it is able to give results similar to FMTK model and experiment, the mean absolute error MAE for rectal temperature prediction was for all ambient temperatures lower than 0.5 °C. FMTK model demonstrated good predictability for impermeable protective clothing Tychem-F, the maximum value of MAE 0.69 °C. Whereas PHS index showed several times larger error, the maximum value higher than 1.8 °C, in the prediction for this type of clothing. The performed simulations showed that the accuracy of the prediction by the PHS index is not so strongly dependent on the value of the overall clothing resistance, but it depends on the value of the moisture permeability index (permeable vs impermeable clothing) which is connected with the water vapor partial pressure under the clothing.