Appropriate assignment of health providers can minimize potential risk to clients and liability for staff nurses, managers, nurse administrators, other providers and health-care agencies. The aim of this study was to assess the relationship between head nurses’ knowledge and practice of nursing assignment and staff nurses 'job satisfaction. Study Setting: This study was carried out at Zagazig University Hospitals. Research Design: Descriptive correlational design was used in this study. The study sample was a purposive sample of 273 staff nurses and a convenient sample of head nurses and their charges (35). Tools of data collection: Three tools were used: (1) nursing assignment knowledge questionnaire, (2) auditing observational checklist, and (3) nurses' satisfaction questionnaire. The result: The findings of this study revealed that the majority (70.1%) of the studied head nurses’ had a good knowledge level on nursing assignment, (62.4%) from head nurses’ had high satisfaction practice level of nursing assignment and more than two thirds (67.8%) of staff nurses’ were satisfied regarding their job. Conclusion: The study concluded that, there was a positive highly statistical significant correlation between head nurses’ knowledge and practice of nursing assignment and staff nurses’ satisfaction toward their job. Recommendation: The study main recommendation was conduct training programs on supervision and communication for head nurse, ensure that the policy and procedures measures work safety related o nursing assignment are followed, enhance nurses’ satisfaction with their nursing assignment and give priority to patients’ needs and acuity, supervision and communication when making nursing assignment.