Worldwide stem cells (SC) donors’ number is still insufficient. To identify the attitudes of Saudi participants regarding their registration to be future donors, a case-control study was conducted at SC donor registration campaigns, King Faisal Hospital, Riyadh. Although (41.7%) of participants were aware of SC, (93%) of them had bad academic knowledge score. More than half of participants (67.3%) were registered as a donor in Saudi Stem Cell Donation Center (SSCDC). Of these participants, (15.5%) knew the Saudi SC donation center. A significant difference was found between registered and non-registered participants regarding age, education level, and knowledge score (P-value≤0.05). The main encouraging attitude was relieving the patient’s pain (65.3%). In conclusion, the majority of Riyadh’s population accepted the idea of SC donation; however, there was a lack of academic knowledge. So that awareness strategies are needed to enhance knowledge, clarify the role of SSCDC, and improve attitudes through correcting wrong ideas.