Objective To study the differential proteins in the malignantly transformed human bronchial epithelial cell line BEP2D induced by α particles and explore the mechanism of radiation-induced lung cancer. Methods The differential proteins were screened by TMT quantitative proteomics and bioinformatics techniques in BEP2D and BERP35T1 cells. Results A total of 52900 unique peptides were identified, and 6128 proteins were quantified. 1910 differential proteins were screened (996 proteins up-regulated and 914 proteins down-regulated). Domain analysis, GO functional analysis, KEGG analysis, and protein-protein interaction network analysis were performed using bioinformatics. 176 domains, 685 GO terms, and 39 KEGG pathways were identified, involving ribosome, NAD, glycolysis/gluconeogenesis, oxidative phosphorylation. Through protein-protein interaction network analysis, the ribosomal proteins were found to have the highest correlation with the radiation-inducing malignancy transformation of BEP2D cells. Conclusion This study indicated that ribosome pathways may play important roles in the malignant transformation of BEP2D induced by radiation, which provided a basis for further research