β-Thalassemia (β-thal) is a public health problem in the Gaza Strip, Palestine, where about 320 patients are currently managed through blood transfusions and iron chelation. Within the restrictive environment of the Gaza Strip, no advanced molecular analysis [sequencing, real-time polymerase chain reaction (real-time PCR)] technology is currently available for developing a premarital screening protocol and providing couples at risk with prenatal diagnosis. Therefore, genetic identification of samples with indicators of β-thal is delayed for weeks before the samples can be sequenced outside the country. As nine causative mutations have been identified in the majority of β-thal cases in the Gaza Strip, a basic genetic screening strategy was designed to improve timeliness in mutation identification and reduce costs to the Palestinian health system. In the present study, we developed a reliable method for the detection of nine Mediterranean β-thal mutations common to the Palestinian population using a panel of restriction enzyme digests. This strategy utilizes standard instrumentation (thermocycler and agarose gel electrophoresis) that would be available in any basic molecular genetics or biochemical laboratory and provides a reliable method of genetic screening and counseling for patients at risk for β-thal.