Abstract: To clarify the effects of smoking cigarette with sweetened tipping paper on the smokers, saliva samples were collected from the control group (KB)and the groups smoking cigarettes with sweetened tipping paper(SK-A)and cigarettes with unsweetened tipping paper(SK-B). The protein levels in the saliva samples were identified and analyzed with quantitative proteomics technology labeled by tandem mass tag (TMT). The results showed that: 1)A total of 2 099 proteins were identified in the samples from the three groups, of which 2 042 proteins were identified in the samples from KB, SK-A and SK-B separately. 2)Compared with KB, there were 107 and 5 differentially expressed proteins identified in the samples from SK-B and SK-A, respectively. Compared with SK-A, there were 59 differentially expressed proteins in the saliva samples from SK-B, including 55 up-regulated proteins and 4 down-regulated proteins. 3)Further bioinformatics analysis was conducted to classify the proteins by gene ontology (GO) and KEGG database. The differentially expressed proteins in SK-B vs SK-A samples were significantly enriched in the biological process of cellular response to chemical stimulus and the molecular function of organic acids binding, which mainly involved the metabolic pathways and drug metabolism-other enzymes pathways. These results suggested that the oral stimulation responses of smokers to cigarettes with unsweetened tipping paper were greater than those to cigarettes with sweetened tipping paper.