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.　©　2022