Abstract: Objective To establish and optimize a method for simultanewus determination for the contents of sodium, potassium,calci-um and magnesium ions in serum using microwave digestion combined with ion chromatography , and evaltate its peformance.MethodsSerum samples were pretreated by microwave dligestion，and four cations were quantitatively detemined using ion chromatography.The linearity , precision, recovery and acuracy of the established method were verified with reference to the EP6-A and EPl5-A3 docu-ments isued by the Clinical and Laboratory Standarls Institute (CLSI).Results The imprecisions of deterninations for sotdium， po-tassium,calcium and magnesium ions expressed as oefficient of variation ( CV) were 0.10% to 0.36% ,0.15%e to 0.48%,0.22% to0.87% and 0.21% to 0.73% ， respectively. The recoveries with adding standard of the four cations were between 97.3% anmd 103.0%.Referred to RELA2020 and RELA2021 , the deviations of the analysis results were -0.57% to -0.14% ，-0.84% to-0.16%，-1.82%6to -0.37% ， and -0.60% to 0.34% for sodium， potassium, calcium , and magnesium ， respectively , and all the comparisons were pae-sed. The limits of detection/ quantification were 0.0175/0.058 3 mmol/L，0.000 5/0.001 7 mmoL,0.009 9/0.032 9 mmol/L and0.001 1/0.003 5 mmol/L for the four cations，indicating that after pretreatment， no significantly interfere from other impurities for theresuls of determinmation was found.Conclusion A method for simultaneous determination of sodium , potassium, calcitm and magnesi-um ions in serum was successhully established and optimizedl using microwave digestion combined with ion chromatography. The methodshowed good precision anmd acuracy , simple operation , shot time consumption and low cost, thus it could be used for quality improve-ment of clinical electrolyte testing in serum.