Background: Organ transplant is considered the treatment of choice for patients with end-stage organ disorders. This process improves recipient’s longevity and quality of life. However, organ shortage for transplantation has remained an unresolved global issue. One of the primary sources of organ donation is brain-dead bodies. The most important factor that impedes the success of donation is lack of family's consent. Exploring effective factors on decision making of the families of brain-dead patients for organ donation helps policy makers plan how to facilitate organ donation. Materials and Methods: A cross-sectional study was conducted with 223 employees and 222 clients of Shohadaye-Khalij-e-Fars Hospital in Bushehr province in 2016. Samples were selected through a proportionate stratified random sampling from each hospital. Knowledge and Attitude towards Organ Donation and Brain Death Questionnaire, developed by Iranian Society of Organ Donation, was used for data collection. Data were analyzed in SPSS 16. Results: Mean scores of employees' knowledge and attitude towards donation were higher than those of hospital clients. However, clients' mean score of religious belief was higher than employees'. There was a significant positive relationship between employees' attitude and religious belief. A significant relationship was also observed between employees' knowledge and probable causes of disagreement with organ donation. Furthermore, the relationship of hospital clients' attitude towards donation with their religious belief, knowledge and probable causes of disagreement with organ donation was significant. The relationship of their knowledge with their religious belief and probable causes of disagreement with organ donation was also significant. Conclusion: Considering that organ donation can save people's lives, the need to train and improve the factors observed in this research is felt to encourage people to donate organs.