Background: The work environment plays a significant role in shaping staff nurses' self-leadership and attitude toward safety. It is essential to recognize the profound impact that the workplace setting can have on staff nurses' ability to exhibit self-leadership qualities and attitudes towards promoting a robust safety culture within the organization. Aim: The current study aims to explore the effect of work environment on staff nurses' perception of self-leadership and attitudes toward safety culture. Research questions: What are staff nurses' perceptions toward their work environment? What are staff nurses' perceptions of self-leadership? What are staff nurses' attitudes towards safety culture?  What is the effect of work environment on staff nurses' perception of self-leadership and attitudes toward safety culture? Design: Descriptive-Correlational research design used in this study. Setting: The current study was conducted at Al kasr El Ainy and Dar El Fouad Hospitals. Sample: Cross-sectional purposive sampling consisted of 200 staff nurse who are working in ICU at governmental and private hospitals. Tools: four tools were used for data collection in this study. Tool one: personal and work-related data Sheet, Tool two: work environment questionnaire, Tool three: Self-leadership questionnaire Tool four: Safety Attitudes Questionnaire. Results: The staff nurses' was highly perceived their work environment in private hospital (78%) and they low perceived it (36%) in governmental hospital, staff nurses' were highly perceived their self-leadership   in governmental hospital (76%) and they moderately perceived it (52%) in private hospital, staff nurses' were highly perceived their attitude toward safety culture in private hospital (96%) and governmental hospital (93%). Conclusion: there was a significant statistical positive correlation (r=0.216, p=0.002) between staff nurses' perception toward their work environment, and perception of self-leadership. There was a highly significant statistical positive correlation (r=-0.345, p=0.00) between staff nurses' perception toward their work environment, and attitude towards safety culture. And also, there was a statistically significance positive effect of work environment on staff nurses' perception of self-leadership (R²=0.05, Beta=0.216, p=0.002) and attitudes toward safety culture (R²=0.12, Beta=0.345, p=0.00). Recommendation: Nurse Manager should focus on providing clear communication channels, supportive leadership, teamwork opportunities, and adequate resources to enhance the workplace environment. Promoting self-leadership skills among nurses through training, feedback mechanisms, and recognition programs can further reinforce nurses' positive attitude toward safety. Also, head nurses should empower staff nurses and provide opportunities for collaboration that can foster self-leadership skills.