Electronic cigarette (e-Cig) has been promoted as a safer alternative to traditional cigarette (t-Cig) recently. However, there are limited scientific data on the potential health effects of e-Cig use. In this study, we evaluated the cytotoxicities of e-Cig and t-Cig condensate solutions (e-CigCS and t-CigCS) on human bronchial epithelial cells (16HBE cells) in vitro, and employed the exosome proteomic technique to systematically assess the effects of e-CigCS and t-CigCS on 16HBE cells. Cytotoxicity assay showed 16HBE cells were more sensitive to t-CigCS than e-CigCS. Proteomic analysis demonstrated that there are 431 differential expressed exosomal proteins (DEEPs) in test groups compared to the control air group (P-value<0.05) and t-CigCS has a greater influence than e-CigCS on exosomal protein expression. Bioinformatic analysis showed the DEEPs from the t-Cig group were significantly enriched in pathways in cancer while tobacco-flavored e-Cig (e-Cigt) and menthol-flavored e-Cig (e-Cigm) groups were not. Further validations of some DEEPs, such as NF-κB p65, Sulfiredoxin-1(SRXN1) and Thioredoxin-interacting protein (TXNIP), were carried out using immunoblot and Real-time PCR analysis, showing that t-Cig may have a greater influence than e-Cig on tumor development and metastasis. Taken together, the finding reported here strongly support our hypothesis that electronic cigarettes are significantly less toxic compared with traditional cigarette.