Abstract: Thalassemia(Thal) is a major hereditary birth defect disease in southern China. As a high-prevalence region for Thal, Guangxi has significantly reduced the birth rate of infants with thalassemia major through a government-led and multi-departmental prevention system integrating premarital and preconception screening, prenatal diagnosis, genetic counseling, and standardized intervention. This experience provides an important model for comprehensive Thal prevention and control. At present, the prevention and control of thalassemia major has entered a new stage focusing on long-term consolidation and quality improvement rather than rapid reduction of affected births alone. Future efforts should continue to move the prevention gateway forward, refine an integrated screening system covering the premarital, preconception, and early pregnancy periods, strengthen closedloop management of screen-positive couples, improve laboratory quality control, enhance genetic counseling capacity, and address regional disparities. Meanwhile, attention should be paid to comprehensive treatment for children already born with thalassemia major, including standardized blood transfusions, iron chelation therapy, hematopoietic stem cell transplantation, and gene therapy, thereby shifting the prevention-and-control system from "preventing new cases" to a model of "preventing new cases, managing existing cases, and pursuing cure". The experience from Guangxi suggests that only the integration of public-health-oriented prevention and clinical treatment can sustainably consolidate the achievements in prevention and control of thalassemia major, and provide a replicable pathway for the comprehensive prevention and treatment of birth defects in China.