Abstract: Objective　To evaluate the free thalassaemia screening programme for preconception and pregnancy in Hainan Province, and to provide a theoretical basis for optimizing the screening process for thalassaemia. Methods From November 2020 to July 2021, a survey was conducted on 10 396 adults with Hainan household registration who participated in the Epidemiological Survey of Thalassemia in Hainan Residents in 19 cities and counties of Hainan Province. All of them underwent routine blood tests, haemoglobin electrophoresis tests and genetic tests for thalassaemia. The optimal diagnostic cut-off values for mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and haemoglobin adult type 2 (HbA2) were determined using screening test indexes such as receiver operating characteristic curve and sensitivity. The diagnostic effectiveness of different primary screening programs for thalassemia gene carriers was evaluated. Results Using the existing MCV single-indicator thalassemia primary screening protocol in Hainan Province, where individuals with MCV<82 fL undergo thalassemia gene testing, resulted in a high missed diagnosis rate (34.06%) and low sensitivity (65.94%). The optimal cut-off values for MCV screening for alpha-and beta-thalassaemia were 84.45 fL and 79.05 fL, respectively; the optimal cut-off values for MCH screening for alpha-and beta-thalassaemia were 27.95 pg and 25.15 pg, respectively. The optimal cut-off value for HbA2 screening for alpha-thalassaemia was less than 2.55% and greater than 3.35% for beta-thalassaemia. The "combined HbA2 or MCH or MCV screening protocol" with the cut-off values recommended in this study had a better performance in primary screening for thalassemia, with the highest sensitivity (92.96%) and negative predictive value (92.67%) and the lowest underdiagnosis rate (7.04%), statistically significant differences compared with the existing protocol (P<0.05). Conclusions The current process of screening for thalassemia in Hainan Province may lead to missed diagnoses. The combined use of MCV, MCH and HbA2 for thalassemia screening, adopting locally suitable cutoff values for primary screening indicators, can improve the incidence of missed reporting of thalassemia and enhance diagnostic effectiveness.