The polymetallic mineral samples in Pan-Xi region are rich in rare earth resources, and exploring an efficient and accurate analysis method is of great significance for their comprehensive utilization. In this study, the samples were decomposed by three methods, namely closed acid dissolution, open acid dissolution with five acid and alkali fusion with sodium peroxide, and the 15 REE were determined by inductively coupled plasma mass spectrometry (ICP-MS) with Rh and Re as internal standard correction elements. The comparative experiments were conducted using standard substances, and the results showed: (1) The detection limit of closed acid dissolution method was low with relative standard deviation (RSD) ranging from 2.51% to 9.56% and the accuracy of method (ΔlgC) ranging from 0.006 to 0.073, while the sample processing was long, and the results of some REE were low. (2) The RSD of open acid dissolution with five acid method ranged from 1.93% to 7.96%, and ΔlgC ranged from 0.004 to 0.045 with low results of the determination results of REE. (3) The alkali fusion with sodium peroxide method eliminated the influence of matrix effects by selecting instrument optimization, sample dilution, appropriate internal standard elements, etc. The RSD ranged from 1.24% to 6.49%, and ΔlgC ranged from 0.001 to 0.032. In conclusion, alkali fusion with sodium peroxide method has a fast analysis process, complete sample dissolution, and the accuracy and precision of test results can meet the requirements of specification (DZ/T0011-2015), which is most suitable for the analysis of REE in polymetallic mineral samples from Pan-Xi region.