Objectives: The aim of this study was to assess the knowledge, attitude and motivation toward stem cell donation among Saudi population in Riyadh, Saudi Arabia. Methods: This is a cross-sectional study that was conducted at different malls in Riyadh. Selection of malls was done randomly according to the geographical distribution of Riyadh, in which sample size was calculated and distributed equally. The participants were asked to complete a questionnaire that addressed their knowledge, attitude and motivation toward stem cell transplantation and donation. Results: Results of this study showed that population knowledge about stem cell transplantation and donation is considered to be low. Only (37.8%) has enough information about stem cell transplantation and donation. There is a positive correlation between level of education and participant’s knowledge regarding stem cell transplantation and donation. The study revealed that 39.3% of participants have willingness for stem cell donation. Conclusion: It has been found that two third of population expressed lack of knowledge about stem cell transplantation and donation. Also, only 40% of participants showed willingness for donation, and the most common reason for not donating stem cell was the lack of information about stem cell and the value of donation While, increasing level of education was associated with better understanding of stem cell donation and its role in therapy and saving lives. Therefore, suitable campaign, advertising and counseling program for population is recommended to increase level of knowledge and motivation toward stem cell donation.