β-Thalassemia, a common genetic disease in Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia, is a major problem of global health (Cao and Galanello, 2010; Galanello and Origa, 2010; Weatherall, 2010). Genetic mutations, which will lead to the reduction of hemoglobin β chain (β-globin) and erythrocytes, finally cause oxygen shortage, bone deformity, organ dysfunction and even organ failure in many parts of the human body (Cao and Galanello, 2010). Based on the severity of the disease, β-thalassemia can be classified into β-thalassemia minor (also called β-thalassemia carrier), β-thalassemia intermedia, and β-thalassemia major (Cooley’s anemia) (Cao and Galanello, 2010). Without treatment, patients with β-thalassemia major usually die before age 5. Thalassemia major patients require lifelong blood transfusion and iron chelation treatment to survive, often accompanied by numerous complications, including arrhythmia, congestive heart failure, hypothyroidism, hypoparathyroidism, hypogonadism, diabetes, osteoporosis, liver cirrhosis, and infection (Chern et al., 2007; Wu et al., 2017). To date, allogeneic bone marrow transplantation (BMT) is the only curative therapy, but BMT is limited by human leukocyte antigen (HLA) compatibility. β-Thalassemia is mainly caused by mutations in the HBB gene, of which −28 (A>G) mutation is a common defect reducing the transcription of HBB (Orkin et al., 1983). Patients with homozygous or compound heterozygous −28 (A>G) mutation may develop severe anemia or intermedia anemia (Cao and Galanello, 2010; Orkin et al., 1983). Correcting the −28 (A>G) mutation by base editing should help to ameliorate anemia. Here, we report the efficient correction of −28 (A>G) mutation in human primary cells and human embryos by base editors.