Background: Healthcare-associated infections (HAIs) significantly threaten patient safety globally, especially in re-source-constrained settings. Hand hygiene (HH) is a critical infection control measure; however, suboptimal compliance persists, contributing to increased healthcare costs and patient morbidity. This study investigated the relationship between pa-tient safety culture and HH compliance in Dakahlia Governo-rate Hospitals in Egypt. Material and Methods: A mixed-methods approach was used. Quantitative data (n=1474) were collected using the Safety Attitudes Questionnaire (SAQ) to assess patient safety culture across six dimensions (teamwork, safety climate, job satisfaction, stress recognition, perceptions of management, and working conditions). The Arabic SAQ underwent rigor-ous translation and cultural adaptation. HH compliance (6300 observed opportunities) was concurrently measured via direct observation using the WHO Hand Hygiene observation tool. Qualitative data were gathered from 50 participants through structured interviews, exploring perceptions and experiences related to HH practices, focusing on management's influence, job satisfaction, workplace challenges, and opportunities for enhancing safety culture. Results: The overall HH compliance rate was 41.43%, varying significantly across hospitals, job roles, and shifts. Quantitative analysis revealed significant positive correlations between HH compliance and Teamwork Climate (r=0.567, p=0.001), Perceptions of Management (r=0.449, p=0.015), Job Satisfaction (r=0.425, p=0.021) and Working Conditions (r=0.472, p=0.01). Nurses exhibited the highest compliance rate, 75%, while other roles, especially support staff, showed lower rates. Qualitative thematic analysis identified key themes: Inconsistent management support and feedback on HH practices; the significant negative impact of high workloads and understaffing on compliance; role-specific challenges and differences in accountability for HH across different job cate-gories; challenges in working conditions and opportunities to improve safety culture. Conclusion: A positive safety culture, particularly strong teamwork, is crucial for HH compliance. However, compliance is multifaceted, influenced by job satisfaction, management support, resource availability, and effective workplace design. Variability across roles necessitates targeted interventions. Recommendations: Enhancing HH compliance requires a multi-pronged approach: Targeted training, improved re-source management, enhanced communication and feedback, team-building initiatives, optimized work environments, and formal recognition programs.