With the emphasis on environment and health, the environmental protection, quality and safety of historical building’s fire-retardant coating has gradually become the focus of attention. There are a lot of volatile substances in the fire-retardant coating, which volatilize continuously for a long time after use, directly affect the air quality and seriously harm people’s health. Therefore, it is of great practical significance to determine harmful substances in historical building’s fire-retardant coating by gas chromatography. The determination is carried out in the way of experiment, including the steps of experimental instrument and reagent, sample formulation, density determination, chromatographic condition, experimental method, gas chromatograph detection, detection method evaluation, and comparative analysis of detection results, etc. The results show that compared with spectrophotometry, electrochemical detection and liquid chromatography, gas chromatography is in content analysis, detection limit, recovery rate of standard addition, relative standard deviation and other aspects should perform better, which proves that gas chromatography has stronger detection performance and is more conducive to the determination of harmful substances in historical building’s fire-retardant coating.