Background: Sickle-cell disease (SCD) is a group of genetic disorders characterized by abnormally shaped red blood cells (RBCs), which are destroyed at increased rates, leading to anemia. Recently, Saudi Arabia has been reported to have an increased prevalence of SCD. Objective: The aim of the present study was to assess perceptions about SCD among the general population in Albaha region, Saudi Arabia, and the possible relationship between their levels of knowledge and socio-demographic characteristics. Methods: The study was carried out on 218 Saudi subjects who completed the self-administered questionnaires during the study period. Results: This study demonstrated that more than two-thirds of the respondents (68.80%) had good knowledge about basics of sickle cell disease. Those with poor knowledge (31.20%) were mainly younger males and works as businessmen and housewives, and all of them had no previous experience with SCD child. Despite the recorded favorable level of knowledge, certain gaps in knowledge were identified; most of them falsely believed that some foods like fava beans, lentils, falafel made with fava beans, vigna and /or nuts could precipitate sickle-cell crisis.Moreover, in depth information of our study population about pattern of inheritance of SCD and its complications were not sufficient. Conclusion: In our study, a good level of awareness regarding SCD was found. Some of the respondents were confused about the nature of inheritance, complications and dietary factors related to the disease. So, community health education meetings and/or media programs to increase the public awareness are recommended.