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Context.Proteins in the saliva are one of the defense mechanism factors that can protect the oral cavity from disease. However, smoking might affect the properties of saliva., Aim: To determine the differences in salivary protein profiles and total concentrations in smokers and non-smokers and their correlation with dental caries severity as indicated by the Decayed, Missing, Filled-Teeth (DMF-T) scores., Methods and Material: This cross-sectional study included 25 smokers and 25 non-smokers. The DMF-T scores were recorded. The total salivary protein was measured by the Bradford method, and the profile proteins were determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)., Results: The average of salivary protein concentration in smokers was lower than that in non-smokers (551.486 µg/mL versus 765.361 µg/mL), but the difference was not statistically significant (P > 0.05). Further correlation analyses showed a negative correlation between the concentration of proteins based on the extent of smoking. A weak negative correlation was found between protein concentration and DMF-T scores (r = -0.239). Dominant salivary protein bands of 11.6 kDa and 54.5 kDa were found in smokers and 27 kDa, 60 kDa, and 94.5 kDa were found in non-smokers., Conclusion: Different protein bands appeared in smokers and non-smokers. There was a weak correlation between protein concentration, DMF-T scores, and the extent of smoking., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)