Background: Statins are proposed as a chemoprevention agent for breast cancer due to their anti-inflammatory effect. The effects of lipophilic and hydrophilic statins on breast cancer risk might be different due to their different pharmacologic properties. Therefore, this study aimed to assess a casual-effect of lipophilic and hydrophilic statins on breast cancer risk using a counterfactual framework approach. Methods: A cross-sectional study of 15,718 women who were screened for breast cancer at Mammographic center, Ramathibodi Hospital, Bangkok, Thailand, was conducted during September 2011 to 2012. A counterfactual framework approach was applied to assess causal effects of treatments (i.e., lipophilic and hydrophilic statins) on outcome (i.e. breast cancer). Multi-logit and logistic regression models were used for treatment and outcome models, respectively. An inverse probability weight regression analysis (IPWRA) was then applied to estimate potential outcome mean (POM) and average treatment effect (ATE) by combining the outcome and treatment models. Results: Breast cancer risks were 0.0072 (95% CI: 0.0055, 0.0089), 0.0051 (95% CI: 0.0008, 0.0095), and 0.0038 (95% CI: 0.002, 0.0056) for non-statin users, hydrophilic, and lipophilic statin users, respectively. The estimated risk differences were -0.0021 (95% CI: -0.0067, 0.0026) and -0.0034 (95% CI: -0.0059, -0.0009) for hydrophilic and lipophilic statins respectively. The number needed to treat for hydrophilic and lipophilic statins were 2.1 (95% CI: -2.6, 6.7) and 3.4 (95% CI: 1.0, 5.9) per 1000 subjected, respectively. Conclusions: Our results suggested that using lipophilic statin could significantly reduce risk of breast cancer in Thai women.