Featured Application: The NISDL method proposed in this paper can be used for real time noninvasively measuring human skin temperature, which reflect human body thermal comfort status and can be used for control HVAC devices.Abstract: In human-centered intelligent building, real-time measurements of human thermal comfort play critical roles and supply feedback control signals for building heating, ventilation, and air conditioning (HVAC) systems. Due to the challenges of intra-and inter-individual differences and skin subtleness variations, there is no satisfactory solution for thermal comfort measurements until now. In this paper, a non-invasive measuring method based on skin sensitivity index and deep learning (NISDL) was proposed to measure real-time skin temperature. A new evaluating index, named skin sensitivity index (SSI), was defined to overcome individual differences and skin subtleness variations. To illustrate the effectiveness of SSI proposed, two multi-layers deep learning framework (NISDL method I and II) was designed and the DenseNet201 was used for extracting features from skin images. The partly personal saturation temperature (NIPST) algorithm was use for algorithm comparisons. Another deep learning algorithm without SSI (DL) was also generated for algorithm comparisons. Finally, a total of 1.44 million image data was used for algorithm validation. The results show that 55.6180% and 52.2472% error values (NISDL method I, II) are scattered at [0 °C, 0.25 °C), and the same error intervals distribution of NIPST is 35.3933%.