Background: Herpes Simplex Virus (HSV) infections, primarily caused by HSV-1 and HSV-2, are prevalent worldwide and carry significant health implications. The impact of tobacco use on HSV infections, however, remains underexplored. Methods: This cross-sectional study utilized the National Health and Nutrition Examination Survey (NHANES) database (2009-2016) to investigate the link between Tobacco use and HSV infections among U.S. adults. Smoking status, volume, and serum cotinine levels were analyzed, alongside demographic and behavioral factors. Propensity score matching (PSM) was employed to adjust for confounders such as sexual behavior. Results: Our study involved 5,693 participants to explore the relationship of tobacco use and HSV infection. We found that smokers, particularly current smokers, have a significantly increased risk of both HSV-1 and HSV-2 infections compared to non-smokers. Specifically, the adjusted odds ratio (OR) for HSV-1 in current smokers was 1.36 (95% CI: 1.16-1.59, p<0.001), and for HSV-2, it was 2.37 (95% CI: 1.88-3, p<0.001). The risk escalates with the intensity of smoking. Elevated serum cotinine levels correlated with an increased risk of HSV infection[HSV-1:1.13 (95% CI:1.09~1.18, p<0.001); HSV-2:1.33 (95% CI:1.25~1.41, p<0.001)]. After propensity score matching (PSM) for factors such as age, gender, sexual behavior, and condom use, these associations remained significant. Conclusion: Tobacco use is significantly associated with an increased risk of HSV infections, highlighting the importance of reducing tobacco exposure in public health strategies against HSV. Further longitudinal studies are warranted to establish causality and explore underlying mechanisms.