Introduction: Breast self-examination is a straightforward, affordable, and uncomplicated approach to identify any alteration in the breast. When conducted correctly, it aids in the early detection of breast cancer and diminishes its impact on health and mortality. It is advised that women aged 20 and above perform self-examinations monthly, consistently. However, the extent of breast self-examination practices in Ethiopia has not been thoroughly documented. Objective: The aim of the study is to identify predictors of breast self-examination practices and associated factors among women aged 20 and above in Sidama Region, South Ethiopia. Methods : -A Cross-sectional study was conducted on 1000 women aged 20-70 years. The study employed a multistage sampling method. Data collection was performed using a structured and pretested interviewer administered questionnaire. The collected data were entered into Epi-data version 3.1 and analyzed by SPSS version 20. Descriptive statistics were used to describe the study population in relation to relevant variables. Bivariate and multivariable logistic regression analyses were conducted to assess the impact of independent variables on the dependent variable. Variables with p-value <0.25 were considered as candidates for multivariable logistic regression. Statistical significance was declared at P < 0.05 and 95% CI. Result:-The prevalence of breast self-examination was found to be 5.2%, with only 46.2% of participants performing it regularly. Factors significantly associated with the practice of BSE among women included were Good knowledge about breast cancer and breast self-examination (Adjusted odds ratio=4.5, 95%CI: 1.4, 14.7), high perceived susceptibility (Adjusted odds Ratio =2.7, 95%CI: 1.4, 5.2), high perceived barrier (Adjusted odds ratio=0.30, 95%CI: 0.11, 0.8) and high perceived self-efficacy (Adjusted odds ratio=3.9, 95%CI: 2.0, 7.7). Conclusion: The study revealed a notably low prevalence of BSE practice among the study population compared to previous study conducted in Ethiopia. Factors such as knowledge about breast cancer and breast self-examination, high perceived susceptibility, and high perceived self-efficacy were identified as significant predictors of BSE practice. To address this issue, collaboration and efforts from various stakeholders including Zonal Health department, District health offices, Health workers, and other relevant parties are needed. It is crucial to focus on raising awareness and improving the perception of women regarding BSE to enhance the currently inadequate practice.