The content of elements in blood and urine samples can effectively reflect the internal exposed information by different pathways. Currently, there are many methods for pretreat method, such as digestion and direct dilution. But these methods have their own weak points. In order to obtain the contents of multi-elements in urine, an analytical method was established for accurate determination of Mn, Co, V, Cu and Zn in urine by using inductively coupled plasma-mass spectrometry (ICP-MS) with kinetic energy discrimination system (KED). The method is improved on the basis of direct dilution method, after the pre-preparation, such as water-bath heating and supersonic, and the 21 inorganic elements in urine samples were determined by ICP-MS. The changes of background equivalent concentration (BEC) for multi-elements in KED mode were optimized in detail. Application of kinetic energy discrimination and collisional cleavage between helium atoms and interfering molecules reduces the influence of mass spectrometry interference such as polyatomic interference on the determination. The matrix effects and signal drift were adjusted by the online addition of internal standards and the standard addition method. The flow rate and rejection parameter q (Rpq)in the KED mode were selected by considering the BEC and the best gas flow rate for He was 3.8 mL·min-1, Rpq=0.45, respectively. The detection limit for the 21 inorganic elements were between 0.004~12.08 μg·L-1, under the optimized conditions. The liner correlation coefficient (R2) of analyzes were ≥0.999 in the range 0~200 μg·L-1. The recovery of all elements ranged from 81.8% to 112.6%, and the relative standard deviation (RSD) was under 5%. The method study research indexes were much lower than the “Simultaneous determination of a variety of metals in urine-Inductively coupled plasma mass spectrometry method”(GBZ/T 308—2018). The method is simple, rapid and accurate, which can be used to determine inorganic elements in urine samples directly, providing a scientific basis for public health emergency and clinical examination.