High Performance Work Practices (HPWP) has not been sufficiently investigated in the frame of Non-profit Organizations. At the same time the need of NPOs for satisfied employees keeps rising, because of the increased demand for their services, especially in the health care sector. The purpose of this thesis is to investigate the relationship between HPWP and the mediation of Work Passion. The survey was based on a quantitative methodological approach, with the use of questionnaires, and the sample was constituted of 125 employees of health and mental health Non-profit Organizations based in Athens. The statistical analysis was implemented with the use of IBM SPSS Statistics 20. It was shown that HPWP are positively related to Work Passion. The implementation of High-Performance Work Practices and the recruitment of employees who share common values with the organization can contribute significantly in this direction, since they are related to higher career satisfaction, through the increase of employee’s work passion.