Skin is the largest organ of human body. Its histological changes may reflect local lesions and serve as the manifestation of systemic diseases. Some molecules in the skin can absorb exciting light of a specific wavelength and emit emission light with a longer wavelength. These molecules are called endogenous fluorophores, and the emission light is called skin autofluorescence (SAF). Different endogenous fluorophore has its specific fluorescence spectrum. When the skin undergoes pathological changes, the content of certain endogenous fluorophores in the skin will change, and even new endogenous fluorophores will be produced. SAF detection technique is a non-invasive, convenient and low-cost optical measurement without toxic side effects, which contains autofluorescence imaging and autofluorescence spectroscopy. It plays a vital and distinctive role in the diagnosis and differential diagnosis of various skin diseases and evaluation of skin pathological changes by analyzing the fluorescence intensity and the excitation or emission spectrum of skin endogenous fluorophores, especially in the early diagnosis of the disease and long-term follow-up after treatment. So far, SAF technology has been used in differential diagnosis of psoriasis, atopic dermatitis, contact dermatitis and other types of inflammatory dermatosis, in monitoring the treatment effect, quantitatively evaluating skin wound healing and scar fibrosis and predicting the type of scar formation, in quantifying and calibrating skin aging and photoaging, in differential diagnosis of multiple types of benign or malignant skin tumors, in guidance of the scope of resection in surgical operations, etc. In addition, SAF produced by advanced glycation end products can also be used as one of the risk grading indicators for various system diseases such as endocrine system, nervous system, cardiovascular system, and urinary system. This article briefly introduces the principle of SAF detection techique, reviews the application of SAF technology to the diagnosis of diseases, supplements the application of other systemic diseases and provides an outlook on the future development of SAF detection technique, in order to provide reference for related medical fields.