Determination of inorganic elements in traditional Chinese medicine by conventional wet-chemistry approach is complex and time-consuming. The samples must be digested before instrumental analysis. For preparations containing cinnabaris or realgar, high content of Hg and As will contaminate lab wares and instruments. However, X-ray fluorescence spectrometry is simple, fast and can simultaneously determine multiple elements in a non-destructive way. In this paper, portable X-ray fluorescence spectrometry was applied to establish a novel method for rapid and nondestructive determination of Hg and As in Niuhuang Qingxin Pills. And the method was employed in homogeneity analysis of the drug for the first time. After optimization of the measurement mode, using the inductively coupled plasma-optical emission spectroscopy as the reference value, working calibration curve was obtained for determination. Experiments results showed that precision was high with relative standard deviation of 0.09% and 0.23%, respectively, and the determination results of Hg and As were close to the reference values with relative mean deviations of 8.58% and 5.95%, respectively, which met the requirements of on-site rapid screening. Results indicated that contents of Hg in 2 batches of the samples were abnormally low and contents of As in 1 batches of the samples was abnormally high. Sample from 1 manufacturer was inhomogeneous. The proposed method was quick, simple, economic and environment-friendly, which offered a new approach for quality control of traditional Chinese medicine containing mineral. The portable instrument brings high efficiency and high throughput, which can help revealing hidden danger of drug quality. In all, X-ray fluorescence spectrometry can save time, manpower and resources, and has a bright prospect in application.