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Background: There may be unexplored interactions between family health, personality, and smoking that could help provide new perspectives on tobacco control., Objective: To examine the relationship between the health of one's family and their smoking habits, as well as investigate the potential influence of personality on this relationship., Methods: For this cross-sectional investigation, a national survey conducted in China in 2022 recruited a total of 21,916 individuals. The Family Health Scale was utilized to assess the health of the family. The 10-item Big Five Inventory scale was utilized to assess the Big five personality traits. The relationship between big five personality, family health, and smoking were investigated using binary and linear logistic regression. The indirect effects mediated by Big five personality were analyzed using mediation analysis with Sobel tests, and the indirect effects were composited using the Karlson-Holm-Breen method., Results: The overall prevalence of smoking in the study population was 14.87%, 26.19% for males and 3.54% for females. Urban and rural smoking prevalence was 13.81% and 16.10% respectively. Binary logistic regression analysis revealed a significant negative relationship between smoking and family health (odds ratio 0.964, 95% CI 0.959, 0.970, P < 0.001) with covariates controlled. The Karlson-Holm-Breen composition facilitated the connection between extraversion (47.81%) and nervousness (52.19%)., Conclusions: Preventive interventions for smoking behavior should prioritize family health and the Big five personality as significant areas to focus on. According to this study, in addition to implementing various interventions for different personalities, family health should be strengthened to reduce smoking behavior., (© 2024. The Author(s).)