Abstract: X-ray Fluorescence Spectrometry (XRF) technique has been applied to the determination of non-metallic minerals such as gypsum. However, the method is limited due to the lack of certified reference materials and the high content of sulfur and easy volatilization loss of sulfur at high temperature. In order to fit the standard calibration curve, synthetic reference materials were prepared by using gypsum certified reference materials, high purity calcium sulfate and other national primary certified reference materials (soils, stream sediments, carbonate). A method for the determination of ten major and minor components (Si, Al, Fe, Ca, Mg, K, Na, Ti, S, Sr) by XRF was proposed. Dilution ratio and melting temperature were optimized and the matrix effect was corrected by a theoretical α coefficient. Results show that gypsum can be completely melted when the dilution ratio was 9:1 and the melting temperature was 1050℃. The detection limits of the method are 4-135 μg/g, and the precision (RSD, n=12) is less than 3.0%; analytical results of certified reference materials were in good agreement with certified values. The synthetic reference materials for the method expand the adaptability of the sample matrix. The lithium tetraborate-lithium metaborate flux in the melting process could be effectively combined with S, suppressing sulfur volatilization. The method is suitable for batch analysis of the gypsum samples with the sulfur content between 12.60% and 51.91%.