Introduction: Tobacco smoking is a very common addiction worldwide and an environmental factor predisposing to periodontal disease. The role of cytokines and chemokines in chronic periodontitis pathogenesis has been previously confirmed. Evaluating serum cytokines and chemokines is essential in determining inflammatory responses in periodontitis patients. Previous findings imply a close relationship between elevated cytokine interleukin-18 (IL-18) levels and chronic periodontitis pathogenesis in smokers; however, the usefulness of IL-18 as an inflammatory marker in gingivitis remains unclear. The aim of the study was to analyze IL-18 levels in smokers with chronic periodontitis. Objectives: The purpose of this study was to analyze the relevance of IL-18 levels to the severity of chronic periodontitis in smokers in terms of the radiographic features of mandibular posterior teeth. Material and methods: A cross-sectional study of 76 male subjects aged 19-34 years with chronic periodontitis in Depok, Indonesia was performed. Clinical data (OHIS, pockets, CAL), smoking status, and IL-18 samples were collected; samples were detected using ELISA. Results: IL-18 levels in smokers with moderate periodontitis were higher than in those with mild periodontitis. However, the results showed that the differences in IL-18 levels were not significant based on daily cigarette consumption, and no significant correlation was revealed regarding IL-18 concentrations in smokers based on smoking duration. The correlation test results demonstrated a significant relationship between periodontitis severity and the number of cigarettes consumed per day, but no significant correlation between periodontitis severity in smokers and smoking duration. Conclusions: IL-18 levels in saliva and gingival crevicular fluid can be used as a predictable biomarker for periodontal disease progression, but cannot be used to determine the patients' smoking habits. Further studies are required to confirm the relationship between IL-18 and chronic periodontitis in smokers.