Global tobacco policies lowered overall and male smoking rates, but female smoking rates have remained unchanged. Parent-child studies revealed the effects of parental smoking, but gender differences had mixed results. We investigated the effects of long-term smoking behavior in families over three generations in order to clarify gender differences. A cross-sectional study in a community-based genome cohort was conducted using a self-reported questionnaire. A total of 8652 respondents were stratified by gender regarding smoking initiation. A logistic regression analysis was performed to analyze the family smoking history. A total of 2987 current smokers and ever-smokers were compared regarding smoking cessation. With respect to smoking initiation, women were affected by their smoking mothers (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.8-3.2) and grandmothers (OR, 1.7; CI, 1.1-2.4). Women who continued smoking were affected only by their smoking mothers (OR, 1.6; CI, 1.05-2.49). In conclusion, gender differences in smoking initiation and cessation are possibly associated with family smoking history. Mothers and grandmothers were shown to have a strong influence on women with respect to both smoking initiation and cessation. Future research should focus on providing evidence for effective gender-specific intervention programs to curb long-term smoking in women.