Background <p>Tobacco use was as an unhealthy lifestyle. But there were few studies about mental and behavioral disorders due to use of tobacco (MBDT). Inflammation played a role in several mental and behavioral disorders. Hence, this research investigated the association between inflammation biomarkers and MBDT.</p> Methods <p>We selected 10 inflammation biomarkers including lymphocyte (LYM), neutrophil (NEU), monocyte (MON), platelet (PLT), aggregate index of systemic inflammation (AISI), systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), platelet-to-Lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) to explore the association between inflammation biomarkers and MBDT in a cross-section study and a dynamic cohort study. To explore the dose-response relationship between inflammation biomarkers MBDT, the restricted cubic spline was performed. Besides, the stratified analyses and sensitive analyses were used to test the stability of results.</p> Results <p>According to results of cohort study, all inflammation biomarkers were significantly associated with the risk of MBDT. The changes in HRs (95%CI) for per SD increment of inflammation biomarkers were as follows: LYM: 1.46 (1.43–1.48); NEU: 1.53 (1.51–1.55); MON: 1.25 (1.23–1.27); PLT: 1.06 (1.04–1.08); AISI: 1.16 (1.14–1.18); SIRI: 1.17 (1.16–1.19); SII: 1.08 (1.06–1.09); LMR: 1.14 (1.12–1.15); NLR: 1.06 (1.05–1.08); PLR: 0.73 (0.72–0.75).</p> Conclusion <p>Higher LYM, NEU, MON, PLT, AISI, SIRI, NLR, LMR and SII may be associated with higher risk of MBDT, and higher PLR may be associated with lower risk of MBDT.</p> Clinical trial number <p>Not applicable.</p>