To explore the toxic effects of rare earth elements (REEs) accumulated in human body, adopting the inductively coupled plasma mass spectrometry (ICP-MS) method, the present study measured REEs and the contents of eight other elements (Ca, Fe, Cu, Na, K, Zn, Mg, and P) in the hair of eight persons exposed to soil containing REEs for a long time as well as in the control group. In addition, proteomic analysis of serum of the two groups was conducted by isobaric tags for relative and absolute quantitation (iTRAQ) technique. Experimental results show that in the hair of the two groups, 15 REEs and eight other elements were detected, in which the content of La, Ce, Pr, Nd, Tb, Ho, Tm, Yb, and Fe in the exposure group is significantly higher than that of the control group, but the content of Ca in the exposure group is significantly lower than that of the control group; analysis yields out 29 differentially expressed proteins, in which 16 proteins are upregulated and 13 proteins are downregulated. Bioinformatics analysis of differentially expressed proteins demonstrates that they participate in various biological processes and five Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, forming an interaction network. Besides, some differentially expressed proteins may be related to neurovirulence, hepatotoxicity, pathological fibrosis, osteoporosis, and anticoagulation caused by REEs. The present experiment investigated the toxic effects of REEs accumulated in human body at the molecular level, which may lay a foundation for the future research of biological effect, threshold limit values, protection from exposure, and reasonable application of REEs.