OBJECTIVE To establish an inductively coupled plasma mass spectrometry (ICP-MS) method for the simultaneous determination of 22 kinds inorganic elements in Broussonetia papyrifera leaves, analyze the differences of inorganic elements in leaves from different origins, and evaluate the safety and health risks of heavy metals and harmful elements, so as to provide a reference for the quality evaluation of Broussonetia papyrifera leaves and the effective development of resources. METHODS After microwave digestion of Broussonetia papyrifera leaves, 22 elements were analyzed by ICP-MS using Relative molecular mass similar elements as internal standards. After methodological investigations, samples were analyzed, and the orthogonal partial least squares discriminant analysis (OPLS-DA) method was utilized to compare variability of inorganic elements from diverse sources. Safety was evaluated by individual pollution index(Pi) and comprehensive pollution index(Pc), while health risk was assessed by calculating maximum daily intake of heavy metals (EDI), target hazard quotient (THQ), and carcinogenic risk (CR). RESULTS The linearity of the 22 elements determined was excellent with a correlation coefficient r²≥0.991. The relative standard deviation (RSD) values of precision, stability, and reproducibility tests met analytical requirements. The detection limit of each element was between 0.000 6 to 1.687 3 μg·L^-1, and recovery rate was between 83.63% and 106.58%. The contents of K, Ca, Mg, and P in 24 batches of leaf samples from different origin were higher, which were 19 098, 5 258, 4 882 and 2 904 mg·kg^-1, respectively. Principal component analysis revealed 5 key factors, identifying Co, Al, Fe, Ni, Sr, Mg, and K as the main characteristic elements of Broussonetia papyrifera leaves. Pi and Pc had excellent safety ratings. EDI and CR results indicated no potential health risks from heavy metals and harmful elements in Broussonetia papyrifera leaves, but THQ suggests that the as element in the leaves may have an impact on human health. CONCLUSION The Broussonetia papyrifera leaves are rich in inorganic elements, heavy metals and harmful elements have less impact on human health, the content of essential elements such as K, Ca, Mg, Fe, Na and Zn are high. This method is sensitive, rapid and accurate for the quantitative analysis of the inorganic elements in Broussonetia papyrifera leaves, which has important value for the study of its inorganic elements.